缬沙坦对糖尿病大鼠一氧化氮及肾脏转化生长因子β1水平的影响

Effects of valsartan on expression of nitric oxide and transforming growth factor-β1 in the glomeruli of diabetic rats

目的:探讨血管紧张素Ⅱ受体拮抗剂缬沙坦对实验性糖尿病大鼠一氧化氮水平及肾皮质转化生长因子β1(TGFβ1)表达的影响。方法:选择健康雄性SD大鼠24只,任取其中16只一次性腹腔注射链脲佐菌素60mg/kg,诱导建立糖尿病模型。将24只大鼠随机分为正常组(NC)、糖尿病模型组(DM)及缬沙坦组(Val)各8只。12周末观察各组大鼠体重、血肌酐、尿素氮、血糖、24h尿蛋白定量。测定血和肾组织一氧化氮(NO),免疫组化检测肾内TGFβ1表达水平及对肾脏标本进行光镜观察。结果:Val组血肌酐、尿蛋白明显低于DM组(P<0.05);血清和肾组织NO水平较降低,下降幅度达79.2%。病理改变轻于DM组,未见有肾小球硬化。结论:缏沙坦对糖尿病大鼠肾脏有明显的保护作用。其作用机制可能是通过增加肾组织局部NO水平和抑制TGFβ1在肾脏的表达,减轻肾脏组织病理损害,从而延缓糖尿病肾病的发生、发展。

Objective：To investigate the effect of angiotensin receptor antagonist Valsartan on the level of nitric oxide （NO） and the expression of and transforming growth factor-β1 （TGFβ1） in renal cortex of diabetic rats. Methods ：Diabetic rats were induced by intraperitoneal Streptozotocin injection （60mg/kg） at one dose. The 24 rats were randomly divided into 3 groups： normal control group（NC）, diabetic model group（DM） and Vasartan-treated diabetic group （Val）. At the end of 12 weeks, body weight, creatinine, uria nitrogen, glucose level of plasma and 24 urinary albumin excretion were detected. NO level in serum and renal tissue was measured. The protein expression of TGFβ1 in renal cortinal was examined by immunohistochemistry. Results： After 12 weeks, the level of serum creatinine and proteinuria in group Val were significantly lower than those in DM group （P〈0.05）. NO level of serum and renal tissue were significantly decreased in Val group compared with those of DM group. Vasartan therapy significantly reduced the expression of renal TGF-β1 in diabetic rats compared with controls. The positive integrated intensity was reduced by about 79.2% in Val group. The pathological changes under light microscopy in Val group were less obvious than that in DM group. Conclusion： Valsartan may have kidney protective effect on diabetic rats, partly through increasing NO level of renal tissue and suppresing the overexpression of TGF-β1, thus decreasing the excretion of urinary albumin and improving the glomerular matrix accumulation and preventing the progression of diabetic nephropathy.