Publications by authors named "Yanting Gu"

14 Publications

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Symptom management to alleviate thirst and dry mouth in critically ill patients: A randomised controlled trial.

Aust Crit Care 2021 Jun 9. Epub 2021 Jun 9.

Department of Critical Care Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Critically ill patients often experience coexisting symptoms. Thirst, in particular, appears to be an important symptom, having the highest prevalence, intensity, and induction of distress, and is significantly correlated with other symptoms. However, thirst and dry mouth are not usually assessed or treated.

Objectives: The aim of the study was to demonstrate the effectiveness of an intervention bundle to relieve thirst and dry mouth.

Methods: The present study was a randomised controlled trial in which critically ill patients were allocated to an experimental or control group. The intervention bundles, including vitamin C sprays, peppermint water mouthwash, and a lip moisturiser, were provided to the experimental group for 3 days, whereas patients in the control group were exposed to the placebo interventions, including saline sprays, 40 °C water mouthwash, and wetting the lips with water.

Results: A total of 61 patients were recruited to the study; 65.6% (n = 41) were men, and the average age was 64.2 ± 16.8 years. The average decrease in thirst intensity and oral mucosa situation scores after the interventions was larger in the experimental group patients relative to controls (1.27 and 0.36 vs. 0.19 and 0.1 points, respectively; p < 0.05). Being male, scoring highly on the Acute Physiology and Chronic Health Evaluation II scale, not receiving diuretics, and having higher serum sodium levels were potential predictors of thirst and oral dryness.

Conclusions: The interventional bundle used in this study was shown to be a promising approach that can relieve thirst intensity and dry mouth, which are pervasively distressful to critically ill patients.

Clinical Trial Registration Numbers: The study was registered on the www.Chictr.org.cn under the identification number ChiCTR1900022873.
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http://dx.doi.org/10.1016/j.aucc.2021.04.002DOI Listing
June 2021

Design, synthesis, and biological evaluation of 5-aminotetrahydroquinoline-based LSD1 inhibitors acting on Asp375.

Arch Pharm (Weinheim) 2021 May 13:e2100102. Epub 2021 May 13.

Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, China.

The abnormal expression of lysine-specific histone demethylase 1 (LSD1) is associated with different cancer types, and LSD1 inhibitory activity seems to have high therapeutic potential in cancer treatment. Here, we report the design, synthesis, and biochemical evaluation of novel 5-aminotetrahydroquinoline-based LSD1 inhibitors. Among them, compounds A6, A8, B1-B5, and C4 showed preferable inhibitory effects on LSD1, with IC  = 0.19-0.82 µM. Several potent compounds were selected to evaluate their antiproliferative activity on A549 cells and MCF-7 cells with a high expression of LSD1. The potential binding modes of the compounds were revealed through molecular docking to rationalize the potency of compounds toward LSD1. Our data recognized that the 5-aminotetrahydroquinoline scaffold may serve as a starting point for developing potent LSD1 inhibitors for cancer therapy.
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http://dx.doi.org/10.1002/ardp.202100102DOI Listing
May 2021

Design, synthesis and biological evaluation of novel benzofuran derivatives as potent LSD1 inhibitors.

Eur J Med Chem 2021 Aug 24;220:113501. Epub 2021 Apr 24.

Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, China.

Lysine-specific demethylase 1 (LSD1) is a FAD-dependent enzyme, which has been proposed as a promising target for therapeutic cancer. Herein, a series of benzofuran derivatives were designed, synthesized and biochemical evaluated as novel LSD1 inhibitors based on scaffold hopping and conformational restriction strategy. Most of the compounds potently suppressed the enzymatic activities of LSD1 and potently inhibited tumor cells proliferation. In particular, the representative compound 17i exhibited excellent LSD1 inhibition at the molecular levels with IC = 0.065 μM, as well as anti-proliferation against MCF-7, MGC-803, H460, A549 and THP-1 tumor cells with IC values of 2.90 ± 0.32, 5.85 ± 0.35, 2.06 ± 0.27, 5.74 ± 1.03 and 6.15 ± 0.49 μM, respectively. The binding modes of these compounds were rationalized by molecular docking. Meanwhile, a preliminary druggability evaluation showed that compound 17i displayed favorable liver microsomal stability and weak inhibitory activity against CYPs at 10 μM. Remarkably, H460 xenograft tumors studies revealed that 17i demonstrated robust in vivo antitumor efficacy without significant side effects. All the results demonstrated that compound 17i could represent a promising lead for further development.
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http://dx.doi.org/10.1016/j.ejmech.2021.113501DOI Listing
August 2021

Lnc00462717 regulates the permeability of the blood-brain tumor barrier through interaction with PTBP1 to inhibit the miR-186-5p/Occludin signaling pathway.

FASEB J 2020 08 5;34(8):9941-9958. Epub 2020 Jul 5.

Department of Physiology, Life Science and Biopharmaceutical Institution, Shenyang Pharmaceutical University, Shenyang, P.R. China.

Blood-brain tumor barrier (BTB) severely restricts the efficient delivery of chemotherapeutic drugs into brain tumor tissue, which is a critical obstacle for glioma treatment. Recently, long noncoding RNAs (lncRNAs) have shown as regulation factors of numerous biological processes. In this study, we identified that Lnc00462717 was upregulated in glioma endothelial cells (GECs), and that knockdown of Lnc00462717 significantly increased the BTB permeability. Both bioinformatics and RNA immunoprecipitation (RIP) results revealed that Lnc00462717 interacts with polypyrimidine tract binding protein (PTBP1). Moreover, overexpression of PTBP1 significantly reversed the increase in BTB permeability caused by siLnc00462717. Furthermore, the binding sites between miR-186 and PTBP1 as well as between miR-186 and 3'UTR of Occludin mRNA were confirmed by RIP and luciferase assays, respectively. And the interaction of Lnc00462717 and PTBP1 significantly facilitated the binding of PTBP1 to 3'UTR of Occludin mRNA and then blocked the miR-186-5p-induced downregulation of Occludin. In addition, we identified that knockdown of Lnc00462717 or overexpression of miR-186-5p increased the accumulation of doxorubicin (Dox) in brain glioma via the ultrafast liquid chromatography-mass spectrometry system (UFLC-MS/MS system) and decreased the intracranial glioma volume in BALB/c nude mice. Taken together, these results show a novel molecular pathway in BTB that may provide a potential innovative strategy for glioma therapy.
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http://dx.doi.org/10.1096/fj.202000045RDOI Listing
August 2020

Salvianolic acid A increases the accumulation of doxorubicin in brain tumors through Caveolae endocytosis.

Neuropharmacology 2020 05 31;167:107980. Epub 2020 Jan 31.

Department of Physiology, Life Science and Biopharmaceutical Institution, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning Province, PR China. Electronic address:

Brain glioma is one of the most common brain tumors in the central nervous system (CNS). The blood-brain tumor barrier (BTB) restricts the delivery of anti-tumor drugs into tumor tissue in the brain. Therefore, improving the transportation of antineoplastic drugs across the BTB is essential to ameliorate treatment of brain tumors. The present study was performed to explore the effect and mechanism of salvianolic acid A (Sal A) on transportation of doxorubicin (Dox) across the BTB in vivo and in vitro. By creating a brain C6 glioma model in rats, we demonstrated that Sal A significantly increased the level of Dox in brain tumor tissue as shown by liquid chromatograph mass spectrometry. Interestingly, we found that Sal A increased transendothelial electrical resistance (TEER) values of the BTB and decreased the permeability of FITC-Dextran (4kD) across the BTB in vitro. Furthermore, the expression of tight junction proteins (TJs) in glioma endothelial cells (GECs) and brain tumor microvessels were also increased, suggesting that Sal A enhanced delivery of Dox across the BTB independent of the paracellular pathway. Next, we detected that Sal A had an effect on transcellular transport of compounds across the BTB. The accumulation of FITC-labeled bovine serum albumin (FITC-BSA) was significantly increased in GECs after treatment with Sal A (10 μM) for 6h, which was inhibited after pre-treatment with methyl-β-cyclodextrin (MβCD) for 30 min. The increased delivery of Dox across the BTB was also reduced after treatment with MβCD. In addition, phosphorylation levels of protein kinase B (PKB) and tyrosine protein kinase-Src family (Src) were increased in the Sal A treatment group. Sal A up-regulated the expression level of the phosphorylation of Caveolin-1 (pCaveolin-1), and this effect was reversed by a PKB or Src inhibitor. Taken together, our study showed for the first time that Sal A facilitated the delivery of antitumor drugs into brain tumor tissues by targeting the PKB/Src/Caveolin-1 signaling pathway.
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http://dx.doi.org/10.1016/j.neuropharm.2020.107980DOI Listing
May 2020

Enhancement of Hydrotropic Fractionation of Poplar Wood using Autohydrolysis and Disk Refining Pretreatment: Morphology and Overall Chemical Characterization.

Polymers (Basel) 2019 Apr 15;11(4). Epub 2019 Apr 15.

School of Materials and Energy, Center of Emerging Material and Technology, Guangdong University of Technology, Guangzhou 510006, China.

Solid acids have been proposed as a hydrolytic agent for wood biomass dissolution. In this work, we presented an environmentally friendly physicochemical treatment to leave behind cellulose, dissolve hemicellulose, and remove lignin from poplar wood. Several pretreatments, such as autohydrolysis and disk refining, were compared to optimize and modify the process. The -toluenesulfonic acid could extract lignin from wood with a small amount of cellulose degradation. Disk refining with subsequent acid hydrolysis (so-called physicochemical treatment) doubled the delignification efficiency. A comprehensive morphology and overall chemical composition were provided. The crystallinity index (CrI) of treated poplar was increased and the chemical structure was changed after physicochemical treatment. Optical microscopy and scanning electron microscopy analysis demonstrated physicochemical treatment affected the morphology of poplar wood by removing lignin and generating fiberization. In general, this work demonstrated this physicochemical method could be a promising fractionation technology for lignocellulosic biomass due to its advantages, such as good selectivity, in removing lignin while preserving cellulose.
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http://dx.doi.org/10.3390/polym11040685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523484PMC
April 2019

Taurine Attenuates Calpain-2 Induction and a Series of Cell Damage via Suppression of NOX-Derived ROS in ARPE-19 Cells.

Oxid Med Cell Longev 2018 29;2018:4596746. Epub 2018 Jul 29.

Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China.

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) are key transmembrane proteins leading to reactive oxygen species (ROS) overproduction. However, the detailed roles of NOXs in retinal pigment epithelial (RPE) cell metabolic stress induced by Earle's balanced salt solution (EBSS) through starvation remain unclear. In this study, we investigated what roles NOXs play in regard to calpain activity, endoplasmic stress (ER), autophagy, and apoptosis during metabolic stress in ARPE-19 cells. We first found that EBSS induced an increase in NOX2, NOX4, p22phox, and NOX5 compared to NOX1. Secondly, suppression of NOXs resulted in reduced ER stress and autophagy, decreased ROS generation, and alleviated cell apoptosis. Thirdly, silencing of NOX4, NOX5, and p22phox resulted in reduced levels of cell damage. However, silencing of NOX1 was unaffected. Finally, taurine critically mediated NOXs in response to EBSS stress. In conclusion, this study demonstrated for the first time that NOX oxidases are the upstream regulators of calpain-2, ER stress, autophagy, and apoptosis. Furthermore, the protective effect of taurine is mediated by the reduction of NOX-derived ROS, leading to sequential suppression of calpain induction, ER stress, autophagy, and apoptosis.
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http://dx.doi.org/10.1155/2018/4596746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6087582PMC
December 2018

miR-132-3p boosts caveolae-mediated transcellular transport in glioma endothelial cells by targeting PTEN/PI3K/PKB/Src/Cav-1 signaling pathway.

FASEB J 2019 01 19;33(1):441-454. Epub 2018 Jul 19.

Department of Physiology, Life Science and Biopharmaceutical Institution, Shenyang Pharmaceutical University, Shenyang, China; and.

Blood-brain tumor barrier (BTB) impedes the transportation of antitumor therapeutic drugs into brain tumors. Its mechanism is still unknown, but learning how to improve the BTB permeability is critical for drug intervention. Recently, microRNAs (miRNAs) have appeared as regulation factors of numerous biologic processes and therapeutic targets of diverse diseases. In this study, we have identified that miR-132-3p is an essential miRNA by increasing the transcellular transport through the BTB. We found that miR-132-3p expression was significantly up-regulated in glioma endothelial cells (GECs). Furthermore we showed that miR132-3p greatly induced the endocytosis of cholera toxin subunit B and FITC-bovine serum albumin and up-regulated the expression of p-PKB, p-Src and Tyr14 phosphorylation of caveolin-1 (p-Cav-1), while phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression was markedly down-regulated in GECs. Our results identify PTEN as a direct and functional downstream target of miR-132-3p, which is involved in the regulation of p-PKB, p-Src, and p-Cav-1. The inhibitors for PI3K and Src significantly reversed the increase of p-Cav-1 induced by miR-132-3p. Moreover, overexpression of PTEN greatly reduced the endocytosis of cholera toxin subunit B and the up-regulation of p-Cav-1 induced by agomiR132-3p, suggesting that miR132-3p increases the endothelial permeability by inhibition of PTEN expression. In addition, miR132-3p significantly increased the delivery of doxorubicin across the BTB in vitro and contributed to the accumulation of doxorubicin within the brain tumor tissue. Our results show that miR-132-3p contributes to the increased permeability of BTB by targeting PTEN/PI3K/PKB/Src/Cav-1, thereby revealing a novel drug target for the treatment of brain gliomas.-Gu, Y., Cai, R., Zhang, C., Xue, Y., Pan, Y., Wang, J., Zhang, Z. miR-132-3p boosts caveolae-mediated transcellular transport in glioma endothelial cells by targeting PTEN/PI3K/PKB/Src/Cav-1 signaling pathway.
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http://dx.doi.org/10.1096/fj.201800095RRDOI Listing
January 2019

Membrane topology of rat sodium-coupled neutral amino acid transporter 2 (SNAT2).

Biochim Biophys Acta Biomembr 2018 Jul 18;1860(7):1460-1469. Epub 2018 Apr 18.

College of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang City 110016, China. Electronic address:

Sodium-coupled neutral amino acid transporter 2 (SNAT2) is a subtype of the amino acid transport system A that is widely expressed in mammalian tissues. It plays critical roles in glutamic acid-glutamine circulation, liver gluconeogenesis and other biological pathway. However, the topology of the SNAT2 amino acid transporter is unknown. Here we identified the topological structure of SNAT2 using bioinformatics analysis, Methoxy-polyethylene glycol maleimide (mPEG-Mal) chemical modification, protease cleavage assays, immunofluorescence and examination of glycosylation. Our results show that SNAT2 contains 11 transmembrane domains (TMDs) with an intracellular N terminus and an extracellular C terminus. Three N-glycosylation sites were verified at the largest extracellular loop. This model is consistent with the previous model of SNAT2 with the exception of a difference in number of glycosylation sites. This is the first time to confirm the SNAT2 membrane topology using experimental methods. Our study on SNAT2 topology provides valuable structural information of one of the solute carrier family 38 (SLC38) members.
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http://dx.doi.org/10.1016/j.bbamem.2018.04.005DOI Listing
July 2018

A278C mutation of dihydropteridine reductase decreases autophagy via mTOR signaling.

Acta Biochim Biophys Sin (Shanghai) 2017 Aug;49(8):706-712

Aviation General Hospital of China Medical University, Beijing 100012, China.

Dihydropteridine reductase (QDPR) plays an important role in the recycling of BH4 and is closely related to oxidative stress. We have previously reported that the overexpression of QDPR in human kidney HEK293T cells significantly protected against oxidative stress, and these beneficial effects were abolished by A278C mutation. To evaluate the effect of wild-type and mutant QDPR on autophagy and its mechanism in HEK293T cells, we constructed the wild-type and mutant QDPR expression plasmids and transfected them into HEK293T cells. Three days later, cells were collected to observe the expression of fusion protein and the intracellular production of reactive oxygen species (ROS). Western blot analysis was employed to evaluate the change of mTOR and ribosomal protein S6 kinase B1 (S6K1) signaling and the expression of LC-I, LC-II, Bcl-1, Bcl-2, p62, and p53. The results showed that the exogenous wild-type QDPR significantly decreased the expression of mTOR and phosphorylation of the mTOR and S6K1. Mutation of QDPR inhibited the regulation of mTOR, suggesting that QDPR is a positive regulator of autophagy via suppressing mTOR signaling. The expressions of p62, LC3-II and Beclin 1 were dramatically enhanced in wild-type QDPR group, which were reversed after QDPR mutation. Additionally, mutation of QDPR altered the upregulation of QDPR on Beclin 2. It is therefore concluded that QDPR appears to play an important role in enhancing autophagy, and its mutation contributes to dysregulation of autophagy.
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http://dx.doi.org/10.1093/abbs/gmx061DOI Listing
August 2017

Yi qi qing re gao attenuates podocyte injury and inhibits vascular endothelial growth factor overexpression in puromycin aminonucleoside rat model.

Evid Based Complement Alternat Med 2014 21;2014:375986. Epub 2014 May 21.

Department of Pharmacology, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, No. 2 Yinghua Dongjie, Hepingli, Beijing 100029, China.

Proteinuria is the hallmark of chronic kidney disease. Podocyte damage underlies the formation of proteinuria, and vascular endothelial growth factor (VEGF) functions as an autocrine/paracrine regulator. Yi Qi Qing Re Gao (YQQRG) has been used to treat proteinuria for more than two decades. The objective of this study was to investigate the protective effect and possible mechanisms of YQQRG on puromycin aminonucleoside (PAN) rat model. Eighty male Sprague-Dawley rats were randomized into sham group, PAN group, PAN + YQQRG group, and PAN + fosinopril group. Treatments were started 7 days before induction of nephrosis (a single intravenous injection of 40 mg/kg PAN) until day 15. 24 h urinary samples were collected on days 5, 9, and 14. The animals were sacrificed on days 3, 10, and 15, respectively. Blood samples and renal tissues were obtained for detection of biochemical and molecular biological parameters. YQQRG significantly reduced proteinuria, elevated serum albumin, and alleviated renal pathological lesions. YQQRG inhibited VEGF-A, nephrin, podocin, and CD2AP mRNA expression and elevated nephrin, podocin, and CD2AP protein levels starting on day 3. In conclusion, YQQRG attenuates podocyte injury in the rat PAN model through downregulation of VEGF-A and restoration of nephrin, podocin, and CD2AP protein expression.
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http://dx.doi.org/10.1155/2014/375986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055581PMC
June 2014

Attenuation of diabetic nephropathy by Chaihuang-Yishen granule through anti-inflammatory mechanism in streptozotocin-induced rat model of diabetics.

J Ethnopharmacol 2014 22;151(1):556-64. Epub 2013 Nov 22.

Department of Pharmacology, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China. Electronic address:

Ethnopharmacological Relevance: Traditional Chinese medical herbs have been used in China for a long time to treat different diseases. Based on traditional Chinese medicine (TCM) principle, Chaihuang-Yishen granule (CHYS) was developed and has been employed clinically to treat chronic kidney disease including diabetic nephropathy (DN). The present study was designed to investigate its mechanism of action in treatment of DN.

Materials And Methods: Diabetic rats were established by having a right uninephrectomy plus a single intraperitoneal injection of STZ. Rats were divided into four groups of sham, diabetes, diabetes with CHYS and diabetes with fosinopril. CHYS and fosinopril were given to rats by gavage for 20 weeks. Samples from blood, urine and kidney were collected for biochemical, histological, immunohistochemical and molecular analyses.

Results: Rats treated with CHYS showed reduced 24h urinary protein excretion, decreased serum TC and TG levels, but CHYS treatment did not affect blood glucose level. Glomerular mesangial expansion and tubulointerstitial fibrosis in diabetic rats were significantly alleviated by CHYS treatment. Moreover, CHYS administration markedly reduced mRNA levels of NF-κB p65 and TGF-β1, as well as decreased protein levels of NF-κB p65, MCP-1, TNF-α and TGF-β1 in the kidney of diabetic rats.

Conclusions: CHYS ameliorates renal injury in diabetic rats through reduction of inflammatory cytokines and their intracellular signaling.
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http://dx.doi.org/10.1016/j.jep.2013.11.020DOI Listing
September 2014

Regulation of transforming growth factor beta 1 gene expression by dihydropteridine reductase in kidney 293T cells.

Biochem Cell Biol 2013 Jun 13;91(3):187-93. Epub 2012 Dec 13.

Academy of Medical Sciences & Peking Union Medical College, Beijing100730, China.

Quinoid dihydropteridine reductase (QDPR) is an enzyme involved in the metabolic pathway of tetrahydrobiopterin (BH4). BH4 is an essential cofactor of nitric oxide synthase (NOS) and can catalyze arginine to citrulline to release nitric oxide. Point mutations of QDPR have been found in the renal cortex of spontaneous Otsuka Long Evans Tokushima Fatty (OLETF) diabetic rats. However, the role of QDPR in DN is not clear. This study investigates the effects of QDPR overexpression and knockdown on gene expression in the kidney. Rat QDPR cDNA was cloned into pcDNA3.1 vector and transfected in human kidney cells (293T). The expression of NOS, transforming growth factor beta 1 (TGF-β1), Smad3, and NADPH oxidase were examined by RT-PCR and Western blot analyses. BH4 was assayed by using ELISA. Expression of QDPR was significantly decreased and TGF-β1 and Smad3 were increased in the renal cortex of diabetic rats. Transfection of QDPR into 293T cells increased the abundance of QDPR in cytoplasm and significantly reduced the expression of TGF-β1, Smad3, and the NADPH oxidases NOX1 and NOX4. Moreover, abundance of neuronal NOS (nNOS) mRNA and BH4 content were significantly increased. Furthermore, inhibition of QDPR resulted in a significant increase in TGF-β1 expression. In conclusion, QDPR might be an important factor mediating diabetic nephropathy through its regulation of TGF-β1/Smad3 signaling and NADPH oxidase.
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http://dx.doi.org/10.1139/bcb-2012-0087DOI Listing
June 2013

[Influence of scorpion alcoholic extraction on mdr1 mRNA and P-gp expression in brain of phenytoin-resistant convulsive rats].

Zhongguo Zhong Yao Za Zhi 2009 Sep;34(17):2223-7

Department of Phannrmacology, Shanxi Medical University, Taiyuan 030001, China.

Objective: To study the anticonvulsive action of scorpion alcoholic extraction (SAE) on phenytoin-resistant convulsive rats made by direct cortical electrical stimulation in order to investigate the mechanism of antagonizing drug-resistance of SAE.

Method: Using the method of implanting microelectrodes in the cortical motor area of the brains of rats where the brain tissue was stimulated frequently by electricity through microelectrodes until igniting and then PHT (0.154 g x kg(-1) x d(-1)) ig for 7 days, We established phenytoin-resistant convulsive rat model. Total 6 groups were set up in the experiment: Normal control group, convulsion model control group (CMCG), phenytoin-resistant convulsion control group (PRCG), verapamil positive control group (VPCG, 0.0385 g x kg(-1)), scorpion alcohol extraction (SAE1, 6.5 g x kg(-1)) and scorpion alcohol extraction (SAE2, 13.0 g x kg(-1)). After ig both doses of SAE (6.5, 13.0 g x kg(-1)), the effects of SAE on the changes of convulsion threshold of phenytoin-resistant convulsive rats were observed. The method of RT-polymerase chain reaction (RT-PCR) was used to detect the changes of mdrl gene expression and the method of immunohistochemistry (SABC) was adopted to determine the changes of P-gp expression.

Result: Both doses of SAE and verapamil (Ver) ig all raised the convulsant threshold of phenytoin-resistant rats (480.38 +/- 18.48) microA, there were statistical differences (P < 0.05) compared to themselves before drugs-treated. PHT was administrated, and mdrl mRNA and P-gp expression in PRCG was much higher than that in CMCG, with significantly statistical difference (P < 0.01); ig both doses of SAE and Ver all decreased mdrl mRNA and P-gp expression compared to PRCG respectively (P < 0.01).

Conclusion: SAE and Ver ig all produce antagonizing action on phenytoin-resistant convulsive rat model. The machanism is related with inhabiting the mdrl mRNA expression and further decreasing the product P-gp.
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September 2009