黄芪甲苷抑制p-130Cas表达缓解糖尿病肾病的作用机制研究  

Astragaloside IV ameliorates diabetic nephropathy by inhibiting p-130Cas expression in podocytes

作　　者：何东元[1] 陈建国[1] 陈宜方[1] 郑志贵[1] HE Dongyuan;CHEN Jianguo;CHEN Yifang;ZHENG Zhigui(Departments of Nephrology of Zhejiang Hospital,Hangzhou 310013,China)

机构地区：[1]浙江医院肾内科,杭州310013

出　　处：《浙江医学》2018年第14期1532-1535,1539,1653,共5页Zhejiang Medical Journal

基　　金：浙江省自然科学基金资助项目(LY14H050004)

摘　　要：目的探讨黄芪甲苷(AS-IV)通过调节p-130Cas表达缓解糖尿病肾病(DN)的作用机制,以期为DN的治疗开辟新途径。方法将条件永生化的小鼠足细胞株分为正常对照组、高糖组、高糖+低剂量AS-IV组、高糖+高剂量AS-IV组,采用Real time-PCR、Western blot法检测各组足细胞p-130Cas mRNA与蛋白表达水平。将SD大鼠随机分为正常对照组、糖尿病组、糖尿病+低剂量AS-IV组、糖尿病+高剂量AS-IV组,每组各10只。链脲霉素65mg/kg单次腹腔注射法建立糖尿病大鼠模型。造模成功后高糖+低剂量AS-IV组、高糖+高剂量AS-IV组AS-IV干预8周,检测干预第4周末、第8周末各组大鼠24h尿白蛋白水平,光镜和电镜下观察第8周末各组大鼠肾脏病理学变化,免疫荧光法检测肾小球足细胞p-130Cas蛋白表达水平。结果高糖组足细胞p-130Cas蛋白与mRNA表达明显上调,AS-IV剂量依赖性抑制高糖诱导的p-130Cas蛋白与mRNA表达上调。糖尿病大鼠24h尿白蛋白水平明显上升,肾小球系膜增生,足细胞足突融合,足细胞p-130Cas蛋白表达明显上调。AS-IV剂量依赖性抑制糖尿病大鼠肾脏足细胞p-130Cas蛋白表达上调,抑制肾小球系膜增生,缓解足细胞足突融合,降低24h尿白蛋白水平,缓解DN。结论 AS-IV可能通过抑制p-130Cas表达上调,抑制高糖诱导的足细胞足突融合,缓解DN。Objective To investigate the protective effects of Astragaloside IV(AS-IV)on diabetic nephropathy and its mechanism in rats. Methods Conditionally immortalized mouse podocytes were randomly divided into normal control group,high glucose group,high glucose with low dose of AS-IV group and high glucose with high dose of AS-IV group.The protein and mRNA expression of p-130Cas in podocytes were determined by Western blot and Real time-PCR respectively.Male SD rats weighing 180 to 220g were randomly divided into normal control group,diabetes group,diabetes with low dose of AS-IV group and diabetes with high dose of AS-IV group.Diabetes was induced by single STZ intraperitoneal injection with the dose of 65mg/kg.At the end of the 4th and 8th week,24h albuminuria of each group were measured;at the end of the 8th week renal pathological changes were evaluated by light and electron microscopy;the protein expression of p-130Cas in podocytes of glomerulus were determined by immunofluorescence. Results The protein and mRNA expression of p130Cas in podocytes increased significantly under high glucose circumstance and was inhibited by AS-IV in a dose-dependent manner.Albuminuria,glomerular mesangial proliferation,foot process effacement and increase of p-130Cas expression in podocytes were observed in diabetic rats and were ameliorated by AS-IV in a dose-dependent manner. Conclusion AS-IV may inhibit podocyte foot process effacement and ameliorate diabetic nephropathy by reverse the abnormal expression of p-130Cas in podocytes.

关 键 词：黄芪甲苷 糖尿病肾病 足细胞 p-130Cas 

分 类 号：R285.5[医药卫生—中药学]