| 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Realtime-PCR、Westernblot法检测各组足细胞p-130CasmRNA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。 |
| 关键词: 黄芪甲苷 糖尿病肾病 足细胞 p-130Cas |
| DOI：10.12056/j.issn.1006-2785.2018.40.14.2018-653 |
| 分类号: |
| 基金项目:浙江省自然科学基金资助项目（LY14H050004） |
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| Astragaloside IV ameliorates diabetic nephropathy by inhibiting p-130Cas expression in podocytes |
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Zhejiang Hospital
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| Abstract: |
| 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. |
| Key words: Astragaloside IV Diabetic nephropathy Podocyte P-130Cas |
