黄芪甲苷对糖尿病肾病大鼠足细胞的影响及其机制研究

目的：探讨黄芪甲苷（AS- IV）对糖尿病肾病（DN）大鼠足细胞的保护作用及其机制，为DN早期防治开辟一条新途径。方法体重180~200g健康雄性SD大鼠45只按配伍法分为正常对照组（NC组）、DN组和AS- IV治疗组（DN＋AS- IV组），链脲佐菌素腹腔注射建立大鼠早期DN模型。DN＋AS- IV组大鼠在造模前2周予AS- IV 10mg/（kg＆#183;d）灌胃预处理至实验结束，共14周。造模后第6、12周末收集并测定24h尿量及尿蛋白；同时各组按抽签法选取5只大鼠测体重，处死大鼠后测血生化指标，取肾组织，光镜观察肾脏病理病理变化，电镜观察足细胞形态变化，肾母细胞瘤抑制基因1（WT1）免疫组织化学染色观察肾小球足细胞密度变化，Western blot法测定大鼠肾皮质α3β1整合素蛋白水平的变化。结果与NC组相比，DN组大鼠血糖和24h尿蛋白增高，肾脏肾小球系膜区增生，足细胞足突融合，肾小球足细胞数量减少，α3β1整合素蛋白水平下降，差异有统计学意义（P＜0.05）。AS- IV可显著改善DN大鼠蛋白尿，抑制肾小球系膜区增生，抑制足细胞足突融合和数目减少，上调α3β1整合素表达。结论 AS- IV对早期DN大鼠足细胞具有保护作用，可能与其上调足细胞α3β1整合素表达相关。

Effect of astragaloside IV on diabetic nephropathy rat podocytes and its mechanism

Objective To investigate the protect effects of astragaloside IV（AS- IV） on diabetic nephropathy rat podocytes and explore its mechanism. Methods Healthy male Sprague- Dawley （SD） rats of 180~200g were randomly divided into normal control group（NC）, diabetic nephropathy group（DN） and diabetic nephropathy with AS- IV treatment group（DN＋AS- IV）. DN was induced by intraperitoneal injection of streptozotocin. AS- IV treatment was started 2 weeks before STZ injection and lasted 14 weeks. 24 hour urine were col ected and 24 hour urinary protein were measured at the end of the 6th,12th week after STZ injec-tion. At the end of 6th and 12th week after STZ injection, rats were sacrificed and the blood samples were col ected for measuring biochemical parameters. The kidneys were harvested for histopathology, immunohistochemistry, electron microscopy and West-ern blot examinations, and the renal pathology, morphological changes of podocytes, podocyte density changes and expression ofα3β1 integrin protein were analyzed. Results In STZ- induced DN rats severe hyperglycemia and proteinuria were devel-oped. Mesangial expansion, increased podocyte loss and decreased integrin α3 and β1 expression were detected in DN rats. Treatment with AS- IV10mg/ （kg＆#183;d） for 14 weeks ameliorated proteinuria and podocyte foot process effacement, attenuated the loss of podocytes in glomerules and up- regulated the expression of integrinα3 andβ1 in podocytes. Conclusion AS- IV may protect podocyte and ameliorate diabetic nephropathy by restoring the expression ofα3β1 integrin in diabetic rats.