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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(P<0.01),VEGF表达明显抑制(P<0.01),其中高剂量组和缬沙坦组效果类似,明显优于低剂量组(P<0.01)。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。
Objective: To study the effect of gypenosides on renal podocyte nephrin and vascular endothelial growth factor (VEGF) mRNA expression in diabetic nephropathy (DN) rats and to explore its mechanism of reducing urinary protein and protecting kidneys. Methods: The model of DN was established by unilateral nephrectomy and streptozotocin (STZ) injection. The experiment was divided into normal group, model group, treatment group (high, medium and low gypenosides) and valsartan group. After 4 weeks of intervention, ultrastructural changes of glomeruli were observed by electron microscope. The expressions of nephrin and VEGF mRNA were detected by RT-PCR. Results: Compared with the model group, the pathological changes in all treatment groups were improved to some extent: the foot process was broadened or partially fused, and the basement membrane thickening was reduced. At the same time, nephrin mRNA expression was significantly up-regulated (P <0.01) and VEGF expression was significantly inhibited (P <0.01). The high-dose group and valsartan group had similar effect, which was obviously better than the low-dose group (P <0.01). Conclusion: Gypenosides may protect podocytes, reduce urinary protein and delay glomerulosclerosis by up-regulating the expression of nephrin, inhibiting the overexpression of VEGF and diminishing the ultrastructure of podocytes.