Publications by authors named "Xi Sheng Xie"

31 Publications

Bunge and Panax notoginseng (Burkill) F.H. Chen Formula for Renal Injury in Diabetic Nephropathy- and Evidence for Autophagy Regulation.

Front Pharmacol 2020 12;11:732. Epub 2020 Jun 12.

Research Center of Combined Traditional Chinese and Western Medicine, Affiliated Traditional Medicine Hospital, Southwest Medical University, Luzhou, China.

Background: Diabetic nephropathy (DN) is a serious complication of diabetes mellitus (DM) with limited treatment options. DN leads to progressive renal failure and accelerates rapidly into end-stage renal disease. Bunge and Panax notoginseng (Burkill) F.H. Chen formula (APF) is a traditional Chinese medicine (TCM) formula widely used to treat chronic kidney diseases (CKD) in the clinic in the southwest of China. The aim of this study is to explore how APF and its related TCM theory work on DN and whether mTOR/PINK1/Parkin signaling plays a part in this process.

Methods: HPLC was used for preliminary chemical analysis and quantitative analysis of the five components of APF. An autophagy deficiency model was established in C57BL/6 mice by streptozocin (STZ) combined with a high-fat and high-sugar diet, while the autophagy deficiency model was induced with high glucose (HG) in renal mesangial cells (RMCs). Renal histopathology staining was performed to investigate the extents of inflammation and injury. Real time-PCR and Western blotting techniques were utilized to assess autophagy-related proteins.

Results: APF significantly ameliorated renal injury in DN mice, specifically restoring blood urea nitrogen, serum creatinine, and 24-hour albuminuria. APF also reduced the mRNA and protein expressions of TNFα, IL-1β, and IL-6 in STZ-induced DN mice. Furthermore, APF improved the autophagy deficiency induced by STZ or HG , as revealed by changes in the expressions of mTOR, PINK1, Parkin, Beclin 1, p62, and LC3B. Notably, inhibition of autophagy with 3-methyladenine in APF-treated RMCs aggravated cellular damage and altered mTOR/PINK1/Parkin signaling, indicating that APF rescued HG damage through promoting autophagy.

Conclusion: APF may protect the kidneys from inflammation injuries in DN by upregulating autophagy suppressing mTOR and activating PINK1/Parkin signaling. This experimental evidence strongly supports APF as a potential option for the prevention and treatment of DN.
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http://dx.doi.org/10.3389/fphar.2020.00732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303297PMC
June 2020

[Investigation on the Influencing Factors of Adult Dyslipidemia in Shunqing District of Nanchong City].

Sichuan Da Xue Xue Bao Yi Xue Ban 2020 Jan;51(1):54-59

Department of Nephrology, the Second Affiliated Medical College (Nanchong Central Hospital) of North Sichuan Medical College, Nanchong 637001, China.

Objective: To analyze the risk factors of dyslipidemia of adult residents in Shunqing District of Nanchong City.

Methods: A five-stage stratified cluster sampling method was used to select adult residents from 9 communities in the urban area of Shunqing District of Nanchong City from January 2013 to April 2018 for questionnaires survey,physical measurement and laboratory test. Univariate analysis and multivariate logistic regression analysis were used to study the influencing factors of dyslipidemia.

Results: A total of 105 956 people was investigated,and the prevalence rate of dyslipidemia was 34.2% (36 272 cases). Among them, the prevalence rate of male was 38.11%, and 31.91% for female ( <0.01). The proportion of dyslipidemia with hypertension, diabetes, and coronary heart disease was 13.46%, 5.74%, and 0.39%, respectively. The proportion of hypertension with diabetes was 2.79%. Multivariate logistic regression analysis showed that gender (odds ratio ( )=1.276, <0.001), body mass index ( =1.052, <0.001), education level (set ≤elementary school as reference, high school =1.094, <0.001, ≥graduated =1.185, <0.001), smoking history ( =1.124, <0.001), coronary heart disease ( =1.189, <0.001), hypertension ( =1.148, <0.001),sdiabetes ( =1.967, <0.001), and family history of dyslipidemia ( =1.760, <0.001) were the influencing factors of dyslipidemia in residents of this region. The dyslipidemia of urban residents in Nanchong area is highly concerned with hypertension, diabetes, and coronary heart disease. Male, obesity, high education level, smoking, coronary heart disease, hypertension, diabetes, and family history of dyslipidemia are risk factors for dyslipidemia in urban residents of Nanchong area. It is necessary to actively target the above risk factors and high-risk groups.
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http://dx.doi.org/10.12182/20200160401DOI Listing
January 2020

Impact of Different Levels of iPTH on All-Cause Mortality in Dialysis Patients with Secondary Hyperparathyroidism after Parathyroidectomy.

Biomed Res Int 2017 5;2017:6934706. Epub 2017 Jun 5.

Department of Nephrology, Cangzhou People's Hospital, Cangzhou, China.

Background: Secondary hyperparathyroidism (SHPT) usually required parathyroidectomy (PTX) when drugs treatment is invalid. Analysis was done on the impact of different intact parathyroid hormone (iPTH) after the PTX on all-cause mortality.

Methods: An open, retrospective, multicenter cohort design was conducted. The sample included 525 dialysis patients with SHPT who had undergone PTX.

Results: 404 patients conformed to the standard, with 36 (8.91%) deaths during the 11 years of follow-up. One week postoperatively, different levels of serum iPTH were divided into four groups: A: ≤20 pg/mL; B: 21-150 pg/mL; C: 151-600 pg/mL; and D: >600 pg/mL. All-cause mortality in groups with different iPTH levels appeared as follows: A (8.29%), B (3.54%), C (10.91%), and D (29.03%). The all-cause mortality of B was the lowest, with D the highest. We used group A as reference (hazard ratio (HR) = 1) compared with the other groups, and HRs on groups B, C, and D appeared as 0.57, 1.43, and 3.45, respectively.

Conclusion: The all-cause mortality was associated with different levels of iPTH after the PTX. We found that iPTH > 600 pg/mL appeared as a factor which increased the risk of all-cause mortality. When iPTH levels were positively and effectively reducing, the risk of all-cause mortality also decreased. The most appropriate level of postoperative iPTH seemed to be 21-150 pg/mL.
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http://dx.doi.org/10.1155/2017/6934706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474544PMC
March 2018

A meta-analysis of the effects of statin treatment on cardiovascular events and all-cause mortality in diabetic dialysis patients.

Int J Clin Exp Med 2015 15;8(6):8415-24. Epub 2015 Jun 15.

Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University No. 100 Haining Road, Hongkou District, Shanghai 200080, China.

Objectives: Diabetic dialysis patients have higher risk of cardiovascular disease (CVD) than general population. While statin treatment is effective in prevention of CVD and all-cause mortality in general population, the use of statin in diabetic dialysis patients remains controversial. Thus, we aimed to assess the effects of statin treatment on prevention of CVD and all-cause mortality in diabetic dialysis patients by meta-analysis.

Materials And Methods: Pubmed, Embase and Cochrane Library were searched between each database's inception and July, 2014. Hazard ratio (HR) with 95% confidence interval (CI) for CVD and all-cause mortality was extracted from each study. The pooled analysis was performed using random-effects models by Stata 12.0.

Results: Our search yielded five eligible articles including two RCTs and three observational studies. By pooled estimate, statin treatment was associated with a decreased risk of the cardiac endpoint which included cardiac death and nonfatal MI (HR=0.84, 95% CI: 0.78-0.90) and all cardiac events combined (HR=0.89, 95% CI: 0.82-0.96). There was no difference in the overall incidence of fatal or nonfatal stroke (HR=1.24, 95% CI: 0.99-1.53) and all cerebrovascular events combined (HR=1.14, 95% CI: 0.98-1.33) between statin treatment and control group. Finally, statin treatment was associated with a decreased risk of all-cause mortality (HR=0.81, 95% CI: 0.71-0.92).

Conclusions: Statin treatment may be beneficial for reducing the risk of cardiac events and all-cause mortality while have no effect on overall cerebrovascular events in diabetic dialysis patients. More RCTs were needed to validate the results.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4538050PMC
August 2015

Androgens for the anaemia of chronic kidney disease in adults.

Cochrane Database Syst Rev 2014 Oct 9(10):CD006881. Epub 2014 Oct 9.

Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Woman's University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul, Korea, South, 120-750.

Background: Anaemia occurs when blood contains fewer red blood cells and lower haemoglobin levels than normal, and is a common complication among adults with chronic kidney disease (CKD). Although a number of approaches are applied to correct anaemia in adults with CKD, the use of androgen therapy is controversial.

Objectives: The aim of this review was to determine the benefits and harms of androgens for the treatment of anaemia in adult patients with CKD.

Search Methods: We searched CENTRAL, the Cochrane Renal Group's Specialised Register, the Chinese Biomedicine Database (CBM), CNKI, VIP and reference lists of articles without language restriction. The most recent search was conducted in August 2014.

Selection Criteria: All randomised controlled trials (RCTs) that assessed the use of androgens for treating anaemia of CKD in adults were eligible for inclusion.

Data Collection And Analysis: Two authors independently extracted data and assessed risk of bias in the included studies. Meta-analyses were performed using relative risk (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI).

Main Results: We included eight studies that reported data from 181 participants. Study quality was assessed as moderate in six studies, one was low quality, and one was high quality. The small number of included studies, and low participant numbers adversely influenced evidence quality overall.We found limited evidence (1 study, 24 participants) to indicate that oxymetholone can increase haemoglobin (Hb) (MD 1.90 g/dL, 95% CI 1.66 to 2.14), haematocrit (HCT) (MD 27.10%, 95% CI 26.49 to 27.71), change in albumin (MD 4.91 g/L, 95% CI 3.69 to 6.13), alanine aminotransferase (ALT) (MD 54.50 U/L, 95% CI 43.94 to 65.06), and aspartate aminotransferase (AST) (MD 47.33 U/L, 95% CI 37.69 to 56.97); and decrease high-density lipoprotein (HDL) (MD -15.66 mg/dL, 95% CI -24.84 to -6.48). We also found that compared with erythropoietin alone, nandrolone decanoate plus erythropoietin may increase HCT (3 studies, 73 participants: MD 2.54%, 95% Cl 0.96 to 4.12). Compared with erythropoietin (1 study, 27 participants), limited evidence was found to suggest that nandrolone decanoate can increase plasma total protein (MD 0.40 g/L, 95% CI 0.13 to 0.67), albumin (MD 0.20 g/L, 95% CI 0.01 to 0.39), and transferrin (MD 45.00 mg/dL, 95% CI 12.61 to 77.39) levels. Compared with no therapy (remnant kidney), evidence was found to suggest that nandrolone decanoate can increase Hb (2 studies, 33 participants: MD 1.04 g/dL, 95% Cl 0.66 to 1.41) and HCT (1 study, 24 participants: MD 3.70%, 95% Cl 0.68 to 6.72). Compared with no therapy (anephric), evidence was found (1 study, 5 participants) to suggest that nandrolone decanoate can increase Hb (MD 1.30 g/dL, 95% Cl 0.57 to 2.03), but nandrolone decanoate did not increase HCT (MD 2.00%, 95% Cl -0.85 to 4.85).However, oxymetholone was not found to reduce blood urea nitrogen (BUN), serum creatinine (SCr), cholesterol, or triglycerides; or increase plasma total protein, prealbumin, or transferrin. No evidence was found to indicate that nandrolone decanoate increased prealbumin or decreased BUN, SCr, AST, ALT, cholesterol, triglycerides, HDL or low-density lipoprotein (LDL). Adverse events associated with androgen therapy were reported infrequently.

Authors' Conclusions: We found insufficient evidence to confirm that use of androgens for adults with CKD-related anaemia is beneficial.
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http://dx.doi.org/10.1002/14651858.CD006881.pub2DOI Listing
October 2014

[Causes of death in STZ-induced rat models of diabetes mellitus].

Sichuan Da Xue Xue Bao Yi Xue Ban 2014 Jul;45(4):691-5

Objective: To identify conditions that may improve the successful rate of STZ-induced rat models of diabetes mellitus (DM).

Methods: 100 male SD rats were randomly divided into control group (n = 10) and experimental group (n = 90). Rats in the experimental group were treated with intraperitoneal injection of STZ 65 mg/kg once, and were then categorized into succeeded DM model group and failed group. Their body masses and levels of fasting blood glucose (FBG), urine glucose (UG), urine protein (UP), urine routine, renal function, liver function, blood lipids and kidney hypertrophy index (KHI) were monitored and compared. Dead rats were dissected to observe diseased organs. Pathological changes of those diseased organs were examined by HE staining.

Results: DM rat models were established through a single intraperitoneal injection of STZ, with a success rate of 58.89%. During the experiment, 43.33% of rats died. Compared with the rats in the failed group, the DM rat models had significantly higher levels of body mass, food intake, water intake, urine output, FBG, creatinine, blood urea nitrogen, KHI, urinary tract infections, and mortality; but lower levels of total protein, albumin and cholesterol and triglyceride (P < 0.05). Nine rats died of pulmonary edema; 19 died of renal abscess. The causes of 11 dead rats were not clear.

Conclusion: DM rat models can be established through a single intraperitoneal injection of STZ 65 mg/kg, but with high mortality rate. The deaths may be associated with infection, malnutrition, suffocation of lymphatic circulation, toxicity of STZ, and changes in environmental and climate conditions.
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July 2014

[Management of chronic kidney disease guided by the theory of Traditional Chinese Medicine: an experimental study].

Sichuan Da Xue Xue Bao Yi Xue Ban 2014 Jan;45(1):34-8

Department of Nephrology, West China Hospital, Sichuan University, Chengdu 610041, China.

Objective: To determine the impact of Traditional Chinese Medicine on patients with chronic kidney disease (CKD).

Methods: A total of 225 CKD patients in an outpatient department were recruited for this study, among whom 170 received regular Western and Chinese medicine treatments (control group) and 55 received treatments guided by the theory of Traditional Chinese Medicine (experimental group). The effectiveness of the treatments was determined through a pre-post comparison.

Results: Significant pre-intervention differences in age (P < 0.01), stage of glomerular filtration rate (GFR) (P = 0.007) and urine protein (P < 0.01) were found between the two groups of patients. But age, gender and proteinuria were not significant predictors on clinical outcomes of the patients in the multivariate regression models. The experimental group had a greater level of decrease in blood urea nitrogen (P < 0.01) and serum creatine (P < 0. 01) than the control group. No significant differences between the groups were found in changes of uric acid (P = 0.475), urine protein (P = 0.058), urine red cells (P = 0.577), and urine white cells (P = 0.01). A greater level of increase in estimated glomerular filtration rate was found in the experimental group compared with the control (P < 0.001). The multivariate linear regression analysis identified group (B = 0.395, P < 0.001) and stage of GFR (B = 0.165, P = 0.008) as significant predictors on the outcomes of treatment.

Conclusion: The treatment of CKD patients guided by the theory of Traditional Chinese Medicine can improve renal function through influencing glomerular filtration rate. The effect is more prominent than the regular treatment regime.
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January 2014

CagA, a major virulence factor of Helicobacter pylori, promotes the production and underglycosylation of IgA1 in DAKIKI cells.

Biochem Biophys Res Commun 2014 Feb 22;444(2):276-81. Epub 2014 Jan 22.

Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500, China; Department of Nephrology, Affiliated Hospital of Luzhou Medical College, Luzhou City 646000, China. Electronic address:

While Helicobacter pylori (Hp) infection is closely associated with IgA nephropathy (IgAN), the underlying molecular mechanisms remain to be elucidated. This study was to investigate the effect of cytotoxin associated gene A protein (CagA), a major virulence factor of Hp, on the production and underglycosylation of IgA1 in the B cell line DAKIKI cells. Cells were cultured and treated with recombinant CagA protein. We found that CagA stimulated cell proliferation and the production of IgA1 in a dose-dependent and time-dependent manner. Moreover, CagA promoted the underglycosylation of IgA1, which at least partly attributed to the downregulation of β1,3-galactosyltransferase (C1GALT1) and its chaperone Cosmc. In conclusion, we demonstrated that Hp infection, at least via CagA, may participate in the pathogenesis of IgAN by influencing the production and glycosylation of IgA1 in B cells.
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http://dx.doi.org/10.1016/j.bbrc.2014.01.050DOI Listing
February 2014

[Investigate the effects of compound radix notoginseng on renal interstitial fibrosis and kidney-targeting treatment].

Sichuan Da Xue Xue Bao Yi Xue Ban 2012 Jan;43(1):28-33

Department of Nephrology, Second Clinical Medical Institution of North Sichuan Medical College (Nanchong Central Hospital), Nanchong 637001, China.

Objective: Investigate the effects of compound Radix Notoginseng on renal interstitial fibrosis and kidney-targeting treatment.

Methods: 100 healthy Sprague-Dawley rats were randomly divided into 5 groups: Unilateral ureteral obstruction (UUO) group, sham-operation (SOR) group, Radix Notoginseng (RN) group, compound Radix Notoginseng (CRN) group and Losartan (ARB) group. After operation, RN, CRN and ARB groups were intragastric administrated with RN (3 mL/d), CRN (3 mL/d) and ARB [20 mg/(kg x d)] respectively. Each group randomly included 18 rats for statistical analysis. The histological changes of renal interstitial tissues were observed by HE, Masson and PAS staining. Total kidney collagen content was determined by measuring the amount of hydroxyproline. The mRNA of alpha-SMA, collagen I and fibronectin were reverse transcribed and quantified by real-time PCR. The expression of alpha-SMA protein was assessed by immunohistochemistry and Western blot analysis.

Results: In UUO model, the obstructed kidney showed typical features of renal tubulointerstitial fibrosis, such as severe tubular loss, dilation, atrophy, infiltration of inflammatory cells, interstitial matrix deposition (P < 0.05). Partial correlation assay showed that the expression of alpha-SMA was related to the renal tubular injury (r = 0.55; P < 0.05). Administration of RN, CRN and ARB improved tubulointerstitial damage and collagen matrix accumulation induced by UUO in different degree. The expression of the alpha-SMA at mRNA and protein levels were significantly increased in the UUO group (P < 0.05), which was also suppressed by treatment with RN, CRN and ARB in different degree. Moreover, more effective role in preventing fibrosis was observed in CRN group than when compared with that of RN group.

Conclusion: RN and CRN can inhibit UUO-induced renal interstitial fibrosis in rats, and CRN treatment is more effective than RN in reducing interstitial fibrosis.
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January 2012

Ginsenoside-Rg1 protects podocytes from complement mediated injury.

J Ethnopharmacol 2011 Sep 29;137(1):99-107. Epub 2011 Apr 29.

Department of Nephrology, West China Hospital of Sichuan University, Chengdu City, Sichuan Province, China.

Aim Of The Study: Podocytes injury mediated by complement complex C5b-9 is the main feature of membranous nephropathy (MN). Little work has been done to prove that ginsenoside-Rg1 could inhibit this process. Our study aims to investigate the efficacy of ginsenoside-Rg1 in protecting the podocyte from complement mediated injury.

Materials And Methods: We chose sublethal C5b-9 induced podocyte injury as the model of MN in vitro. Ginsenoside-Rg1 was given as an intervention. Morphological changes were observed by electron microscope and fluorescence microscope. The production of reactive oxygen species (ROS) was detected by flow cytometry. The expression of the mitogen activated protein kinase (MAPK) including JNK, ERK and P38 was detected by western-blot technique.

Results: Ginsenoside-Rg1 could protect foot processes of podocytes, suppress the damage of F-actin, decrease the production of ROS, and inhibit the activation of P38 kinase pathway.

Conclusion: These results suggest that ginsenoside-Rg1 could protect podocyte from sMAC-induced injury partly because of its antioxidant property and inhibit the activation of P38 kinase pathway.
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http://dx.doi.org/10.1016/j.jep.2011.04.045DOI Listing
September 2011

Ginsenoside Rg1 modulation on thrombospondin-1 and vascular endothelial growth factor expression in early renal fibrogenesis in unilateral obstruction.

Phytother Res 2010 Nov;24(11):1581-7

Department of Nephrology, West China Hospital of Sichuan University, No. 37, Guoxuexiang, Wuhou, Chengdu 610041, China.

Renal interstitial fibrosis is the major histopathological change seen in a variety of renal disorders and is closely related to renal dysfunction. Progressive interstitial fibrosis accompanied by the loss of renal tubules and interstitial capillaries typifies all progressive renal disease. Thrombospondin-1 (TSP-1) is a major angiogenic inhibitor. It is demonstrated that TSP-1 levels were correlated with the loss of glomerular and peritubular capillaries and TSP-1 could promote renal scarring by effects on the endothelium. It has been reported that ginsenoside Rg1 inhibited renal interstitial fibrosis in rats via suppressing the expression of TSP-1. The present study was designed to examine whether ginsenoside Rg1 could modulate the integrity of the microvasculature and hence affect the progression of renal fibrosis in a rat unilateral ureteral obstruction (UUO) model. In UUO control kidneys, associated with interstitial fibrosis, lower peritubular capillary densities were prominent. These changes were all improved by ginsenoside Rg1 treatment. Interestingly, ginsenoside Rg1 decreased the expression of TSP-1 and enhanced vascular endothelial growth factor (VEGF) expression. The results show for the first time that ginsenoside Rg1 can evidently inhibit renal interstitial fibrosis in rats with UUO. The mechanism might be related to suppression of the expression of TSP-1 and to repair of the peritubular capillary.
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http://dx.doi.org/10.1002/ptr.3190DOI Listing
November 2010

[Transforming growth TGF-beta1 mediates the expression of stromal cell derived factor-1 in kidney interstitial fibroblast cells in rats].

Sichuan Da Xue Xue Bao Yi Xue Ban 2010 May;41(3):453-7, 475

Department of Nephrology, West China Hospital, Sichuan University, Chengdu 610041, China.

Objective: To study the expression pattern of SDF-1 in the NRK49F cells and the role of TGF-beta1 in mediating the expression of SDF-1.

Methods: The SDF-1 mRNA and protein expression in the NRK49F cells with or without stimulating by TGF-beta1 was assayed with RT-PCR or Western blot or Immunohistochemistry.

Results: The SDF-1 mRNA expression stimulated by TGF-beta1 appeared in a time-dependent manner. The peak value appeared at 24 hours and was (2.924 +/- 0.235) times as high as the initial level. The dose-course studies suggested that TGF-beta1 stimulation resulted in marked promotion of SDF-1 mRNA expression, which peaked at the concentration of 5 ng/mL. At this concentration, the expression of SDF-1 mRNA was (2.113 +/- 0.314) times as high as that of the control. Corresponding with the pattern of mRNA expression of SDF-1, protein expression of SDF-1 was observed in NRK49F cells. A time-dependent manner was also observed in the protein expression of SDF-1 stimulated by 5 ng/mL of TGF-beta1. The protein expression of SDF-1 at 36 hours was (2.572 +/- 0.238) times as high as that of the control. TGF-beta1 neutralizing antibody reduced the expression of SDF-1 protein.

Conclusion: SDF-1 expresses in NRK49F cells. TGF-beta1 up-regulates the mRNA and protein expressions of SDF-1 in NRK49F cells in a time- and concentration-dependent manner. As a chemokine, the increased expression of SDF-1 induced by TGF-beta1 may play an important role in renal inflammation and fibrosis.
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May 2010

[Leukemia inhibitory factor suppresses renal interstitial fibroblast activation induced by transforming growth factor].

Sichuan Da Xue Xue Bao Yi Xue Ban 2010 May;41(3):448-52

Department of Nephrology, West China Hospital, Sichuan University, Chengdu 610041, China.

Objective: To investigate the effects of leukemia inhibitory factor (LIF) on renal interstitial fibroblast activation following induction by transforming growth factor beta 1 (TGF-beta1).

Methods: Normal rat interstitial fibroblast cells (NRK/49F) were treated with TGF-beta1 and TGF-beta1, combining with LIF respectively for different duration with different concentration. Changes in cell morphology and expression of alpha-SMA were evaluated with electronic microscope and Western blot respectively. The collagen I in the supernatant was detected with ABC-ELISA.

Results: TGF-beta1 induced renal interstitial fibroblast activation, and this was accompanied by significant morphological transformations and secretion of collagen I. Co-culturing of cells with LIF blocked the morphological transformation. In addition, LIF inhibited TGF-beta1-induced expression of alpha-SMA mRNA and protein (P < 0.01), and decreased the levels of collagen I (P < 0.01) in a dose-dependent manner.

Conclusion: LIF suppresses TGF-beta1-induced activation and collagen I secretion of cultured renal interstitial fibroblasts.
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May 2010

[Effects of salidroside on tubular epithelial to myofibroblast transition under cobaltous chloride induced hypoxic status].

Sichuan Da Xue Xue Bao Yi Xue Ban 2010 Jan;41(1):43-8

Department of Nephrology , West China Hospital , Sichuan University, Chengdu, China.

Objective: To investigate the effect and possible mechanism of salidroside on the transdifferentiation of normal rat kidney tubular epithelia cells (NRK52E) under cobaltous chloride (Co) induced hypoxic status.

Methods: Cultured NRK52E cells were divided into control group, Co group and Co plus salidroside treatment groups at a dosage of 10 micromol/L, 50 micromol/L, and 100 micromol/L. Hypoxia-inducible factor-1alpha (HIF-1alpha), a master regulator of oxygen homeostasis was measured as a marker of hypoxic status. Morphologic alteration of cells was observed by inverted phase contrast microscope. The expression of alpha-SMA in NRK52E cells was detected by fluorescent immunocytochemistry (FICC) and immunohistochemistry (IHC). The alpha-SMA and TGF-beta1 mRNA were assessed using reverse transcription-polymerase chain reaction (RT-PCR). The expressions of HIF-1alpha and alpha-SMA protein were detected by Western blot analyses. The enzyme-linked immunosorbent assay was performed to detect collagen I (Col-I) and fibronectin (FN) in the supernatant.

Results: The expression of HIF-1alpha in NRK52E cells was induced by 100 micromol/L of Co in vitro. Co induced transdifferentiation of NRK52E cells, showing fibroblast-like in morphology. Salidroside partly blocked morphologic transformation of tubular epithelial cells. Salidroside decreased the expressions of alpha-SMA protein and mRNA and TGF-beta1 mRNA significantly (P < 0.05), although they were still higher than the controls (P <0 .05). Salidroside, especially in high dosage, inhibited the increase in Col-I and FN induced by Co (P < 0.05).

Conclusion: Hypoxia can induce tubular epithelial-myofibroblast transdifferentiation (TEMT). Salidroside improves Co-induced hypoxic status and inhibits TEMT possibly through reducing Col I and FN in NRK52E cells.
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January 2010

LSKL, a peptide antagonist of thrombospondin-1, attenuates renal interstitial fibrosis in rats with unilateral ureteral obstruction.

Arch Pharm Res 2010 Feb 24;33(2):275-84. Epub 2010 Feb 24.

Department of Nephrology, West China Hospital of Sichuan University, No.37, Guoxuexiang, Wuhou, Chengdu 610041, China.

The effects of LSKL, the peptide antagonist of thrombospondin-1 (TSP-1), on renal interstitial fibrosis in rats subjected to unilateral ureteral obstruction (UUO) were investigated. Rats were divided randomly into three groups (n = 20 each): UUO group, sham-operation group and UUO plus LSKL treatment group. Collagen deposition was studied using histopathology and reverse transcription polymerase chain reaction analysis (RT-PCR). TSP-1, transforming growth factor beta 1 (TGF-beta1), phosphorylated Smad2 (pSsmad2) and alpha-smooth muscle actin (alpha-SMA) in the kidney were measured using immunocytochemistry, western blotting analysis, RT-PCR and enzyme-linked immunosorbent assay. Biochemical analyses in the serum and urine were made. Histopathology showed severe tubular dilatation and atrophy, interstitial inflammation and collagen accumulation after surgery and LSKL significantly inhibited interstitial fibrosis including tubular injury as well as collagen deposition. The protein and mRNA levels of TSP-1 increased notably at different time point and significantly decreased in the presence of LSKL. The expression of TGF-beta1 and pSmad2 were upregulated in the obstructed kidney and substantially suppressed by LSKL treatment. Myofibroblast accumulation could be alleviated after administration of LSKL. Biochemical parameters did not show differences among the three groups. As TSP-1 is the major activator of TGF-beta1, we demonstrate that LSKL can attenuate renal interstitial fibrosis in vivo by preventing TSP-1-mediated TGF-beta1 activation.
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http://dx.doi.org/10.1007/s12272-010-0213-6DOI Listing
February 2010

The role of C1GALT1C1 in lipopolysaccharide-induced IgA1 aberrant O-glycosylation in IgA nephropathy.

Clin Invest Med 2010 Feb 1;33(1):E5-13. Epub 2010 Feb 1.

Department of Nephrology, West China Hospital of Sichuan University, Chengdu City, Sichuan Province, China.

Purpose: IgA1 aberrant O-glycosylation is one of the main pathogenetic features of IgA nephropathy (IgAN). This study attempted to determine the role of C1GALT1C1 in aberrant IgA1 O-glycosylation induced by lipopolysaccharide (LPS) and identify potential therapeutic targets in IgAN.

Methods: Lymphocytes isolated from 22 patients with IgAN and 17 normal controls were cultured for 3 to 7 days with or without LPS and 5-azacytidine (5-AZA). Expression levels of C1GALT1C1 mRNA and protein were measured by real-time PCR and Western blot analysis, respectively. Concentration of IgA1 and level of O-glycosylation were determined by ELISA and Vicia villosa (VV) lectin-binding assay. Correlation analysis was performed between the expression of C1GALT1C1 protein and IgA1 O-glycosylation.

Results: Lymphocytes from patients with IgAN secreted more IgA1 than that from normal controls after LPS stimulation (P=0.26, 0.002 and 0.005 on the 3rd, 5th and 7th day, respectively) which could be inhibited by 5-AZA (P=0.001, 0.025 and 0.001 on the 3rd, 5th and 7th day, respectively). Moreover, LPS stimulation could obviously inhibit C1GALT1C1 expression in patients with IgAN (decreased by 71%, 82% and 92% on the 3rd, 5th and 7th day, respectively; P < 0.001), and cause a significant decrease of IgA1 O-glycosylation compared with normal controls (P=0.004, 0.003 and 0.03 on the 3rd, 5th and 7th day, respectively). When 5-AZA was added, the level of C1GALT1C1 expression increased dramatically (1.98, 5.53 and 8.97 times on the 3rd, 5th and 7th day, respectively; P < 0.001) along with an increase of IgA1 O-glycosylation (P=0.295, 0.09 and 0.003 on the 3rd, 5th and 7th day, respectively). However, normal controls showed no significant change in C1GALT1C1 expression and IgA1 O-glycosylation after LPS stimulation (P > 0.05).

Conclusion: LPS induced IgA1 aberrant O-glycosylation and suppressed C1GALT1C1 expression in patients with IgAN. Upregulation of C1GALT1C1 expression by 5-AZA could reverse the IgA1 aberrant O-glycosylation. These results suggest that C1GALT1C1 may play a key role in the regulation of IgA1 O-glycosylation.
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http://dx.doi.org/10.25011/cim.v33i1.11832DOI Listing
February 2010

Hydraulic pressure inducing renal tubular epithelial-myofibroblast transdifferentiation in vitro.

J Zhejiang Univ Sci B 2009 Sep;10(9):659-67

Department of Nephrology, West China Hospital of Sichuan University, Chengdu 610041, China.

Objective: The effects of hydraulic pressure on renal tubular epithelial-myofibroblast transdifferentiation (TEMT) were investigated.

Methods: We applied hydraulic pressure (50 cm H2O) to normal rat kidney tubular epithelial cells (NRK52E) for different durations. Furthermore, different pressure magnitudes were applied to cells. The morphology, cytoskeleton, and expression of myofibroblastic marker protein and transforming growth factor-beta1 (TGF-beta1) of NRK52E cells were examined.

Results: Disorganized actin filaments and formation of curling clusters in actin were seen in the cytoplasm of pressurized cells. We verified that de novo expression of alpha-smooth muscle actin induced by pressure, which indicated TEMT, was dependent on both the magnitude and duration of pressure. TGF-beta1 expression was significantly upregulated under certain conditions, which implies that the induction of TEMT by hydraulic pressure is related with TGF-beta1.

Conclusion: We illustrate for the first time that hydraulic pressure can induce TEMT in a pressure magnitude- and duration-dependent manner, and that this TEMT is accompanied by TGF-beta1 secretion.
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http://dx.doi.org/10.1631/jzus.B0920110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2738835PMC
September 2009

[Effect of ginsenoside Rgl on the expression of TNF-alpha and MCP-1 in rats with diabetic nephropathy].

Sichuan Da Xue Xue Bao Yi Xue Ban 2009 May;40(3):466-71

Department of Nephrology, State Key Laboratory of Biotherapy of Human Disease, West China Hospital, Sichuan University, Chengdu 610041, China.

Objective: To investigate the effects of Ginsenoside Rgl on proteinuria and the expression of monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) in rats with diabetic nephropathy (DN).

Methods: The DN rat model was established by injection of streptozotocin (STZ, 65 mg/kg) in abdominal cavity. Forty Sprague-Dawley male rats were randomly divided into 4 groups: normal group, DN group, Ginsenoside Rgl treatment group and Irbesartan treatment group. The blood glucose was monitored routinely. Twenty-four hours urine protein and serum creatine were measured the day before the rats were killed when the eight weeks of treatments had been completed. The renal pathological and podocyte changes were evaluated. Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were performed to examine the protein expression levels of MCP-1 and TNF-alpha, respectively. The mRNA of TNF-alpha and MCP-1 were reverse transcribed and quantified by real-time PCR.

Results: The DN rats had increased volume of renal glomerulus, thickened basement membrane, and increased mesenterium mass, as well as some inflammatory cells in renal glomerulus. The number of potocyte decreased significantly in the DN group compared with the normal group (P<0.01). Compared with the DN group, the basement membrane became thinning and the number of podocyte increased in the two treatment groups (P<0.05). The rats in the DN group and the two treatment groups had significantly higher levels of twenty-four hour urine protein, serum creatine, serum glucose, serum MCP-1 and TNF-alpha than the normal rats (P<0.05). The rats in the treatment groups had lower levels of twenty-four hours urine protein and serum creatine than the rats in the DN group (P<0.05). But the serum glucose had little changes (P>0.05). There was no difference between the two treatment groups. Immunohistochemisty, ELISA and real-time PCR results indicated that the expression levels of MCP-1 and TNF-alpha in the rats in the DN group and the two treatment groups were significantly higher than those in the normal group (P<0.05). The rats in the treatment groups had lower levels of expression of MCP-1 and TNF-alpha than those in the DN group (P<0.05). The correlation analysis indicated that the levels of MCP-1 and TNF-alpha were positively related to twenty-four hours urine protein (r=0.7802, 0.6963), glomerular sclerosis index (r=0.8296, 0.7413) and thickness of podocyte membrane (r=0.7678, 0.6701, P<0.05).

Conclusion: Ginsenoside Rgl reduces the expression of MCP-1 and TNF-alpha, repairs the pathological lesions of podocyte and nephron, and reduces the twenty-four hour urine protein rats with diabetic nephropathy.
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May 2009

Astragalus mongholicus ameliorates renal fibrosis by modulating HGF and TGF-beta in rats with unilateral ureteral obstruction.

J Zhejiang Univ Sci B 2009 May;10(5):380-90

Department of Nephrology, West China Hospital of Sichuan University, Chengdu 610041, China.

Astragalus mongholicus (AM) derived from the dry root of Astragalus membranaceus Bge. var. mongolicus (Bge.) Hsiao is a widely used traditional Chinese medicine. The present study investigated the potential role of AM on renal fibrosis on a rat model of unilateral ureteral obstruction (UUO). We divided 48 Sprague-Dawley rats randomly into 4 groups: sham-operated group (Sham), untreated UUO group, AM-treated (10 g/(kg x d)) UUO group, and losartan-treated (20 mg/(kg x d)) UUO group as positive control. Haematoxylin & eosin (HE) and Masson staining were used to study the dynamic histological changes of the kidneys 7 and 14 d after operation. The expressions of fibronectin (FN), type I collagen (colI), hepatocyte growth factor (HGF), transforming growth factor-beta1 (TGF-beta1), and alpha-smooth muscle actin (alpha-SMA) were analyzed by real-time polymerase chain reaction (PCR), immunohistochemistry staining, and Western blot. Results show that, similar to losartan, AM alleviated the renal damage and decreased the deposition of FN and colI from UUO by reducing the expressions of TGF-beta1 and alpha-SMA (P<0.05), whereas HGF increased greatly with AM treatment (P<0.05). Our findings reveal that AM could retard the progression of renal fibrosis. The renoprotective effect of AM might be related to inhibition of myofibroblast activation, inducing of HGF and reducing of TGF-beta1 expression.
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http://dx.doi.org/10.1631/jzus.B0820230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2676418PMC
May 2009

Ginsenoside Rb1, a panoxadiol saponin against oxidative damage and renal interstitial fibrosis in rats with unilateral ureteral obstruction.

Chin J Integr Med 2009 Apr 29;15(2):133-40. Epub 2009 Apr 29.

Department of Nephrology, West China Hospital, Sichuan University, Chengdu, 610041, China.

Objective: To investigate the possible protective effect and mechanism of ginsenoside Rb1 against oxidative damage and renal interstitial fibrosis on rats with unilateral ureteral obstruction (UUO).

Methods: In total, 80 male rats were randomly divided into 4 groups, 20 in each group: the sham operated group (SOR), UUO group, UUO with ginsenoside Rb1 treatment group (treated with intraperitoneal injection of 50 mg/ kg daily) and UUO with Losartan treatment group (as the positive control, treated with 20 mg/kg by gastrogavage per day). The rats were randomly sacrificed on day 3, 7 and 14 after surgery, respectively. The histopathologic changes of renal interstitial tissues were observed with Masson staining. The mRNA of transforming growth factor beta 1 (TGF-beta 1), collagen I and fibronectin were reversed transcribed and quantified by Real-time PCR. Enzyme-linked immunosorbent assay was used to quantitatively detect TGF-beta 1 and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. P47phox protein expression was assessed by immunohistochemistry and Western blot analysis.

Results: In the UUO model, the obstructed kidney showed typical features of progressive renal tubulointerstitial fibrosis, and the levels of TGF-beta1, collagen I and fibronectin increased (P<0.05). As compared with the UUO group, ginsennoside Rb1 significantly inhibited the interstitial fibrosis including tubular injury and collagen deposition, and decreased the levels of TGF-beta1 (P<0.05). Ginsenoside Rb1 also inhibited the heme oxygenase (HO-1) and 8-OHdG, two markers of oxidative stress (P<0.05). Moreover, ginsenoside Rb1 suppressed the expression of p47phox, a subunit of nicotinamide adeninedinucleotide phosphate (NADPH) oxidase (P<0.05).

Conclusion: Ginsenoside Rb1 can obviously inhibit renal interstitial fibrosis in rats with UUO, its mechanism possibly via against the oxidative damage and suppressing TGF-beta1 expression.
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http://dx.doi.org/10.1007/s11655-009-0133-9DOI Listing
April 2009

[Effects of ginsenoside Rb1 on TGF-beta1 induced p47phox expression and extracellular matrix accumulation in rat renal tubular epethelial cells].

Sichuan Da Xue Xue Bao Yi Xue Ban 2009 Jan;40(1):106-10

Department of Nephrology, West China Hospital, Sichuan University, Chengdu 610041, China.

Objective: To investigate the effects of Ginsenoside Rb1 (G-Rb1) on the oxidative damage and extracellular matrix accumulation in rat renal tubular epethelial cells induced by transforming growth factor-beta1 (TGF-beta1).

Methods: Cultured normal rat renal tubular epethelial cells (NRK-52E) were divided into control group, 10 ng/mL TGF-beta1-induced group, G-Rb1 treated groups in which rat renal tubular epethelial cells were treated with different concentration of G-Rb1 (10 ng/mL, 20 ng/mL, 40 ng/mL) after TGF-beta1 induction, G-Rb1 40 ng/mL group and 100 nmol/L DPI(diphenyleneiodonium, an inhibitor of NADPH oxidase) group. Intracellular reactive oxidative species (ROS) level was measured by flowcytometry. p47phox protein expression was assessed by immunohistochemistry and western blotting method. The expressions of collagen I (Col-I) and fibronectin(FN) gene were measured by real-time PCR analysis. The protein level of Col-I and FN were quantitatively detected by enzyme-linked immunosorbent assay.

Results: TGF-beta1 at 10 ng/mL significantly increased the intercellular ROS production and p47phox expression (P < 0.05). The levels of Col-I and FN were also significantly up-regulated with the stimulation of 10 ng/mL TGF-beta1 (P < 0.05). Compared to TGF-beta1-induced group, G-Rb1 and DPI depressed TGF-beta1-induced ROS production and p47phox overexpression. Meanhile, G-Rb1 and DPI decreased the levels of Col-I and FN.

Conclusion: G-Rb1 could inhibit TGF-beta1 induced ROS production and decrease the levels of Col-I and FN in a dose-dependent manner. The mechanism might be partly related to the suppression of p47phox expression.
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January 2009

[Effect of Astragalus mongholicus on expression of hepatocyte growth factor in SD rats with unilateral ureteral obstruction].

Sichuan Da Xue Xue Bao Yi Xue Ban 2009 Jan;40(1):100-5

Department of Nephrology, West China Hospital, Sichuan University, Chengdu 610041, China.

Objective: To study the effect of Astragalus mongholicus (AM) on the expression of hepatocyte growth factor (HGF) in SD rats with unilateral ureteral obstruction (UUO) and to elucidate the mechanisms underlying the renoprotective effects of AM.

Methods: Fifty four Sprague-Dawley rats were randomly divided into 3 groups: sham-operation group (SOR), UUO group (UUO) and UUO + AM group (AM). After administration of AM[10 g/ (kg x d)] for 3, 7 and 14 days,the histological changes of renal interstitial tissues were observed dynamically, and renal damage including tubular impairment and interstitial fibrosis were quantified on HE and Masson stained tissue sections. The protein expression of HGF and alpha-smooth muscle actin (alpha-SMA) was measured by immunohistochemistry. The mRNA expression of HGF and alpha-SMA were determined by real-time PCR. The expression of HGF and its receptor (C-met) were assessed by Western blot.

Results: Renal damage was exacerbated and the expression of alpha-SMA was significantly increased in UUO group compared with those of SOR group (P < 0.05) at each time point. HGF and C-met expression peaked at the 7th day after UUO and then decreased greatly. After AM intervention, tubular impairment and interstitial fibrosis were alleviated, up-regulations of alpha-SMA expressions was significantly suppressed, whileas the expression of HGF and C-met were significantly increased when compared with UUO group (P < 0. 05) at each time point.

Conclusion: AM can ameliorate renal interstitial fibrosis induced by UUO in rats. The mechanisms of its antifibrotic effects may be related with the up-regulation of HGF and C-met expression, and the suppression of tubulo-epithelial mesenchymal transdifferentiation in renal intersitial progress.
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January 2009

[Effect of Astragalus mongholicus on expression of connective tissue growth factor in kidney of SD rats with unilateral ureteral obstruction].

Zhong Yao Cai 2008 Aug;31(8):1185-90

Department of Nephrology, West China Hospital of Sichuan University, Chengdu 610041, China.

Objective: To study the effect of Astrangalus mongholicus (AM) on the expression of Connective Tissue Growth Factor (CTGF) in SD rats with Unilateral Ureteral Obstruction (UUO) and elucidate the mechanism underlying the renorotective effects of AM.

Methods: 36 Sprague-Dawley rats were randomly divided into 3 groups: sham-operation group (Sham), UUO group (UUO) and UUO + AM group (AM). After administration of AM (10 g/kg x d) for 7 and 14 days, the dynamic histological changes of renal interstitial tissues were observed and renal damage including tubular impairment and interstitial fibrosis were quantified on HE and Masson stained tissue sections. The expressions of CTGF and alpha-smooth muscle actin (alpha-SMA) were measured by immunohistochemistry staining sections. The mRNA of CTGF and alpha-SMA were reversely transcribed and quantified to real-time PCR. The expression of CTGF protein was assessed by Western blot.

Results: Renal damage was exacerbated and the expressions of alpha-SMA and CTGF significantly increased in UUO group compared with those of Sham group (P < 0.05) at each time point. Tubular impairment and interstitial fibrosis were alleviated, and up-regulations of expressions of CTGF and alpha-SMA were significantly depressed by AM treatment (P < 0.05).

Conclusions: AM can ameliorate renal interstitial fibrosis induced by UUO in rats. The mechanism of its antifibrotic effects may be related to the down-regulation of CTGF expression, following suppression of tubulo-epithelial mesenchymal transdifferentation in renal intersitial progress.
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August 2008

Ginsenoside Rg1, a major active component isolated from Panax notoginseng, restrains tubular epithelial to myofibroblast transition in vitro.

J Ethnopharmacol 2009 Feb 3;122(1):35-41. Epub 2008 Dec 3.

Department of Nephrology, West China Hospital of Sichuan University, No. 37, Guoxuexiang, Wuhou, Chengdu 610041, China.

The medicinal herb, Panax notoginseng, has been used for thousands of years in traditional Chinese medicine and possesses anti-fibrosis properties. Epithelial-myofibroblast transition (EMT) plays an important role in renal tubulointerstitial fibrosis. The present study was designed to examine whether ginsenoside Rg1, a major active component isolated from Panax notoginseng, has an ability to block this phenotypic transition in rat renal tubular epithelial cells (NRK-52E) induced by transforming growth factor-beta1 (TGF-beta1). The morphology of tubular epithelial-myofibroblast transition was observed through light microscope and transmission electron microscopy. alpha-SMA and E-cadherin are two markers of tubular epithelial-myofibroblast transition, their protein expressions were assessed by immunohistochemistry and western blot analysis. Gene expression of alpha-SMA as well as the two major extracellular matrix components collagen I and fibronectin was measured by real-time PCR analysis. Enzyme-linked immunosorbent assay was used to quantitatively detect collagen I and fibronectin in the supernatant. Our results revealed that ginsenoside Rg1 obviously blocked morphologic transformation in NRK-52E induced by TGF-beta1. Meanwhile, ginsenoside Rg1 inhibited the expression of alpha-SMA and the loss of E-cadherin, subsequently decreased the levels of collagen I and fibronectin in a dose-dependent manner. In addition, western blot analysis indicated that ginsenoside Rg1 inhibited the expression of P-ERK1/2 in NRK-52E induced by TGF-beta1. These results suggest that ginsenoside Rg1 can restrain the process of EMT maybe via suppressing the expression of P-ERK1/2 in vitro.
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http://dx.doi.org/10.1016/j.jep.2008.11.020DOI Listing
February 2009

[Ginsenoside R(g1) inhibit transdifferentiation in rat renal tubular epethelial cells induced by TGF-beta1].

Zhongguo Zhong Yao Za Zhi 2008 Sep;33(17):2136-41

Department of Nephrology, West China Hospital of Sichuan University, Chengdu 610041, China.

Objective: To investigate the effects of ginsenoside R(g1) on the transdifferentiation of rat renal tubular epethelial cells induced by transforming growth factor-beta1, (TGF-beta1).

Method: Cultured normal rat renal tubular epethelial cells (NRK-52E) were divided into control group, TGF-beta1-induced group and treated with ginsenoside R(g1) at different concentration (10, 20, 40 mg x L(-1)) group. The morphology of tubular epithelial-myofibroblast transdifferentiation induced by TGF-beta1 was observed through light microscope. alpha-SMA and E-cadherin protein expression were assessed by immunohistochemistry and western blot analyses. alpha-SMA, collagen I and and fibronectin gene expression were assessed by real-time quantitative chain reaction. Enzyme-linked immunosorbent assay was used to quantitatively detect collagen I and fibronectin in the supernatant.

Result: 10 mg x L(-1) TGF-beta1 could induce the transdifferentiation of tubular epithelial myofibroblast, showing fibroblast-like in morphology, with significantly enhanced expression of alpha-SMA, depressed expression of E-cadherin and increased secretion of fibronectin and collagen I (P < 0.05). Compared to TGF-beta1-induced group, ginsenoside R(g1) partly abrogated the alpha-SMA expression and E-cadherin depression triggered by TGF-beta1 in tubular epithelial cells in a dose-dependent manner (P < 0.05). Meanhile, ginsenoside R(g1) blocked morphologic transformation of tubular epithelial cells and decreased levels of collagen I and fibronectin (P < 0.05).

Conclusion: Ginsenoside R(g1) could inhibit TGF-beta1 induced the tubular epithelial-myofibroblast transdifferentiation and decreased levels of collagen I and fibronectin in NRK52E.
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September 2008

[Effects of piperazine ferulate on TGF-beta1-induced renal interstitial fibroblast activation].

Sichuan Da Xue Xue Bao Yi Xue Ban 2008 Sep;39(5):736-9, 762

Department of Nephrology, West China Hospital, Sichuan University, Chengdu 610041, China.

Objective: To investigate the effects of piperazine ferulate (PF) on TGF-beta1-induced renal interstitial fibroblast activation, and to explore the mechanism of PF in the prevention of renal tubulointerstitial fibrosis.

Methods: In cultured normal rat renal kidney fibroblast (NRK-49F), the effect of PF on the TGF-beta1-induced cell vitality was observed by MTT. The protein expression levels of a-smooth muscle actin (alpha-SMA), connective tissue growth factor (CTGF) induced by TGF-beta1 were evaluated by immunocytochemistry. The levels of a-SMA, CTGF mRNA expression induced by TGF-beta1, were determined by quantitative real time fluroscent polymerase chain reaction. The levels of collagen type I (Col I) and fibronectin (FN) protein expression were examined by Enzyme Linked Immunosorbent Assay(ELISA).

Results: TGF-beta1 may markedly increase the cell vitality, alpha-SMA and CTGF expression, FN and Col I protein expression (P < 0.05). Compared with TGF-beta1-induced group, PF can partly decrease the cell vitality, level of alpha-SMA and CTGF expression and extracellular matrix(ECM) synthesis induced by TGF-beta1 (P < 0.05).

Conclusion: PF may inhibit TGF-beta1-induced fibrosis in the renal fibroblast to a certain extent.
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September 2008

[Effects of piperazine ferulate on connective tissue growth factor and extracellular matrix in TGF-beta1 induced mesangial cells].

Sichuan Da Xue Xue Bao Yi Xue Ban 2008 Sep;39(5):732-5

Department of Nephrology, West China Hospital, Sichuan University, Chengdu, China.

Objective: To observe the effects of piperazine ferulate (PF) on synthesis of extracellular matrix and expression of connective tissue growth factor (CTGF) in transforming growth factor-betal (TGF-beta1) induced rat glomerular mesangial cells (GMC), and to investigate its mechanism on the prevention of glomerulosclerosis.

Methods: Rat HBZY-1 GMCs were cultured in vitro and divided into 5 groups: Normal control group, TGF-beta1-stimulated group, TGF-beta1 plus 50, 100, 200 ng/mL PF group. The level of CTGF protein expression induced by TGF-beta1 was measured by immunocytochemistry, The mRNA expression of CTGF was evaluated by quantitative real time fluroscent polymerase chain reaction. The expressions of fibronectin and collagen I were analyzed by enzyme linked immunosorbent assay (ELISA).

Results: With the stimulation of TGF-beta1, the expression of of CTGF protein and mRNA, as well as fibronectin and collagen I were markly increased (P < 0.05), which then were decreased by the treatment of PF. (P < 0.05).

Conclusion: PF can partly inhibit synthesis of the extracellular matrix and CTGF. PF may take part in the prevention of glomerulosclerosis through the inhibition of CTGF expression.
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September 2008

Influence of ginsenoside Rg1, a panaxatriol saponin from Panax notoginseng, on renal fibrosis in rats with unilateral ureteral obstruction.

J Zhejiang Univ Sci B 2008 Nov;9(11):885-94

Department of Nephrology, West China Hospital, Sichuan University, Chengdu 610041, China.

Total saponins of Panax notoginseng (PNS) have been shown to ameliorate renal interstitial fibrosis. Ginsenoside Rg1, a panaxatriol saponin, is one of the major active molecules from PNS. The present study was undertaken to investigate the effect of ginsenoside Rg1 on renal fibrosis in rats with unilateral ureteral obstruction (UUO). The rats were randomly divided into 3 groups: sham-operation (n=15), UUO (n=15) and UUO with ginsenoside Rg1 treatment (n=15, 50 mg per kg body weight, intraperitoneally (i.p.) injected). The rats were sacrificed on Days 7 and 14 after the surgery. Histological examination demonstrated that ginsenoside Rg1 significantly inhibited interstitial fibrosis including tubular injury as well as collagen deposition. alpha-smooth muscle actin (alpha-SMA) and E-cadherin are two markers of tubular epithelial-myofibroblast transition (TEMT). Interestingly, ginsenoside Rg1 notably decreased alpha-SMA expression and simultaneously enhanced E-cadherin expression. The messenger RNA (mRNA) of transforming growth factor-beta1 (TGF-beta1), a key mediator to regulate TEMT, in the obstructed kidney increased dramatically, but was found to decrease significantly after administration of ginsenoside Rg1. Further study showed that ginsenoside Rg1 considerably decreased the levels of both active TGF-beta1 and phosphorylated Smad2 (pSmad2). Moreover, ginsenoside Rg1 substantially suppressed the expression of thrombospondin-1 (TSP-1), a cytokine which can promote the transcription of TGF-beta1 mRNA and the activation of latent TGF-beta1. These results suggest that ginsenoside Rg1 inhibits renal interstitial fibrosis in rats with UUO. The mechanism might be partly related to the blocking of TEMT via suppressing the expression of TSP-1.
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http://dx.doi.org/10.1631/jzus.B0820024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2579952PMC
November 2008

[The effect of ginsenoside Rg1 on the renal interstitial fibrosis of UUO rat].

Sichuan Da Xue Xue Bao Yi Xue Ban 2008 Mar;39(2):218-22

Department of Nephrology, West China Hospital, Sichuan University, Chengdu 610041, China.

Objective: To study the effect of ginsenoside Rg1 on the renal interstitial fibrosis caused by unilateral ureteral obstruction (UUO) of rats.

Methods: 80 healthy Sprague-Dawley rats were randomly divided into 4 groups: the UUO group (UUO), sham-operation group (SOR), ginsenoside Rg1 group (Rg1) and losartan group (ARB). From the first day after initial UUO, ARB group was intragastrically administrated with losartan 20 mg/(kg x d). UUO, Rg1 and SOR groups were intragastrically administrated with identical volume of normal saline. Rg1 group was intraperitoneally injected with ginsenoside Rg1 50 mg/(kg x d). UUO, ARB and SOR groups were intraperitoneally injected with identical volume of normal saline. At day 3, 7, 14 after UUO, 6 rats selected randomly from each group were killed. The dynamic histological changes of renal interstitial tissues were observed by HE, Masson and PAS staining. The mRNA of transforming growth factor-beta1 (TGF-beta1) was quantified by real-time PCR. The protein levels of TGF-beta1 expression were assessed by Western blot and immunohistochemical method respectively.

Results: In UUO kidneys, the interstitial fibrosis including tubular atrophy, loss and dilation, inflammatory cell infiltration and interstitial matrix deposition was prominent. However, these morphological changes were notably reduced in Rg1 and ARB groups, and there was no significant difference between the two groups (P > 0.05). TGF-beta1 mRNA and protein expression were increased dramatically for UUO group at postoperative day 7 and 14 (P < 0.05). TGF-beta1 expression in Rg1 and ARB groups were significantly lower than that in UUO group (P < 0.05).

Conclusion: Ginsenoside Rg1 can evidently inhibit UUO-induced renal interstitial fibrosis in rat, which may be related to the down regulation of TGF-beta1 expression.
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March 2008

A case report of an effective treatment for diabetic foot ulcers with integration of traditional Chinese medicine and Western medicine.

J Diabetes Complications 2009 Sep-Oct;23(5):360-4. Epub 2008 Jul 3.

Department of Nephrology, West China Hospital of Sichuan University, Guoxuexiang, Wuhou, Chengdu 610041, China.

Diabetes contributes 75-85% of the factors predisposing to foot amputations, usually in association with infection and gangrene. The treatment of foot ulcers is expensive, and the effectiveness of treatment varies. We report herein a case of a diabetic foot ulcer that was treated with integrated traditional Chinese and Western medicine, with desirable cost-effective results. Traditional Chinese medicine (TCM) therapeutic principles include improving the spleen, nourishing yin, regulating qi, and resolving dampness, as well as activating stagnant blood. Western medicine includes wound debridement, skin grafting, and use of insulin, antibiotics, and vasodilators. The patient was treated with a holistic multidisciplinary approach (i.e., a combination of TCM and Western medicine, surgical management, education for diabetic foot care, and psychological counseling). Without this approach, the patient might have ended up with foot amputation and/or sepsis.
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http://dx.doi.org/10.1016/j.jdiacomp.2008.05.002DOI Listing
January 2010
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