血管紧张素受体拮抗剂缬沙坦对糖尿病大鼠肾脏的保护作用

探讨血管紧张素受体拮抗缬沙坦对糖尿病大鼠肾脏病变的保护作用及其机制。方法将实验动物分为正常对照组,糖尿病组及缬沙坦疗组。检测各组第２、４、８周的平均动脉压,血糖、血胰岛素,血肌酐、尿白蛋白、肾组织血管紧张素转换酶活性、血管紧张素Ⅱ含量及肾脏肥大指标的变化。

Renal protective effect of valsartan in diabetic rats

OBJECTIVE: To investigate the mechanism of valsartan in protecting the renal lesion of diabetic rats. METHODS: The following groups of rats were studied: normal control rats, streptozotocin diabetic rats and diabetic rats treated with valsartan (8 mg x kg(-1) x d(-1)). Mean arterial pressure, plasma glucose, serum insulin, serum creatinine, urinary albumin, ACE activity and Ang II concentration of kidney as well as profile of kidney hypertrophy were observed after 2, 4, 8 weeks of treatment, while TGF beta(1) mRNA expression of kidney cortex was assessed by Northern blot analysis, TGF beta(1), fibronectin and collagen IV expression were measured by immunohistochemistry. RESULTS: Serum creatinine level (P < 0.05), urinary albumin excretion and kidney hypertrophy index (P < 0.01) of valsartan treated group were significantly lower than those of diabetic untreated group. There was a significant increase in mRNA expression of TGF beta(1) and protein expression of of TGF beta(1) fibronectin and collagen IV in diabetic rats (P < 0.01). The expression of TGF beta(1) mRNA and protein (P < 0.01) as well as the protein expression of fibronectin and collagen IV (P < 0.05) in the valsartan group were much lower than that in the diabetic group. CONCLUSION: The results suggested that valsartan has some renal protective effect on diabetes in rats, partly through down-regulating TGF beta(1) expression and reducing deposition of glomerular ECM.