绞股蓝总皂苷对糖尿病肾病大鼠足细胞损伤的影响及机制

目的:研究绞股蓝总皂苷对糖尿病肾病(DN)大鼠肾脏足细胞相关分子(nephrin)、血管通透因子(VEGF)mRNA表达的影响,探讨其降低尿蛋白、保护肾脏的机制。方法:采用单侧肾切除加链脲佐菌素(STZ)注射法改良复制DN模型,实验分为正常组、模型组、治疗组(绞股蓝总皂苷高、中、低剂量组)和缬沙坦组。干预4周后电镜观察肾小球超微结构改变,RT-PCR检测nephrin、VEGF mRNA表达。结果:各治疗组病理变化较模型组均有不同程度改善:足突增宽或部分融合,基底膜增厚减轻,同时nephrin mRNA表达水平较模型组明显上调(P0.01),VEGF表达明显抑制(P0.01),其中高剂量组和缬沙坦组效果类似,明显优于低剂量组(P0.01)。结论:绞股蓝总皂苷可能通过上调足细胞相关分子nephrin表达,抑制分泌VEGF过表达,减轻足细胞超微结构改变,从而保护足细胞,降低尿蛋白,延缓肾小球硬化。

Effect of gypenoside on the podocyte injury and its mechanism in rats with diabetic nephropathy

Objective: To investigate the effect of gypenoside on the expressions of nephrin,vascular endothelial growth factor(VEGF) in rats with diabetic nephropathy(DN) and explore its mechanism of the reduction of proteinuria and renal protection.Methods: DN model was established by uninephrectomized and induced with streptozotocin(STZ),then randomly divided into model group and treatment groups(groups of high,medium,low dose of gypenoside,and valsartan group),with normal rats as the control group.All the rats received daily gavage for 4 weeks,and then the ultramicrostructure changes of the glomerulus were observed with transmission electron microscope.The expressions of Nephrin,VEGF mRNA in the podocytes were detected by real-time quantitative PCR.Results: Comparing to the model group,the pathological changes of every treatment groups were improved in different degree: the extension and fusion of foot processes and the thickness of glomerular basement membrane were all ameliorated.Simultaneously,the expression of nephrin mRNA in treatment groups were upregulated as compared to control group(P<0.01),while VEGF mRNA expression significantly inhibited(P<0.01).The result in high dose group was much better than low dose group(P<0.01) and similar to valsartan group.Conclusion: Gypenoside can provide renal protection,reduce proteinuria against glomerulosclerosis in rats and alleviate the ultramicrostructure damages of podocytes possibly by reducing VEGF in expression and increasing nephrin expression the podocytes.