缬沙坦及苯那普利对5/6肾切除大鼠肾小球硬化的影响

Effects of valsartan and benazepril on glomerulosclerosis in rats with 5/6 nephrectomy

目的 :观察并比较缬沙坦及苯那普利对 5 6肾切除大鼠肾小球硬化的改善作用 ,探讨其作用机制。方法 :选用SD雄性大鼠 30只 ,通过 5 6肾切除法制造慢性肾功能衰竭模型 ,术后 2周随机分为模型组、缬沙坦组及苯那普利组 ,并设假手术组作为对照。术后第 6周末各组大鼠进行体重、血压、血清肌酐 (Scr)及尿素氮 (BUN)的测定 ,处死大鼠 ,取出肾组织进行病理组织形态学观察 ,并采用免疫组织化学方法检测肾组织转化生长因子 β1(TGF β1)、IV型胶原、纤维连接蛋白 (FN)表达。结果 :同模型组相比 ,两治疗组收缩压下降 (P均 <0 .0 1) ,肾功能改善 ;肾小球系膜增殖程度、肾小球硬化指数 (GSI)降低 (P均 <0 .0 1) ;免疫组化染色显示 ,两治疗组肾小球转化生长因子 β1(TGF β1)、纤维连接蛋白 (FN)及IV型胶原表达均较模型组下降 (P均 <0 .0 1)。结论 :缬沙坦及苯那普利对慢性肾功能衰竭大鼠具有同等的肾脏保护作用 ;改善肾小球硬化是通过减少肾小球TGF β1表达 ,从而减少FN及IV型胶原生成来实现的。

AIM: To observe and compare the improvement of glomerul- osclerosis in rats with 5/6 nephrectomy by valsartan and benazepril. METHODS: Thirty Sprague-Dawley male rats were selected and performed five-sixths nephrectomy to produce chronic renal failure model. Two weeks after the surgery, the rats were randomly divided into model group, valsartan group and benazepril group, and established a shame group serving as normal control. The weight, blood pressure, blood uria nitrogen (BUN) and serum creatinine were measured on the sixth week after operation, then the rats were killed to take the kidneys for pathological histological observation. Immunohistochemistry was used to examine the expression of TGF-β 1 protein and fibronectin (FN) and collagen IV in glomeruli. RESULTS: As compared with model group, systolic pressure decreased (P< 0.01) and renal function was ameliorated in two treatment groups, as well as the extent of glomerular mesangial proliferation, glomerulosclerosis index(GSI)decreased significantly (P< 0.01). Immunohistochemistry staining indicated that there was an decreasing expression of TGF-β 1, FN and collagen IV in glomeruli in two treatment groups compared with model group (P< 0.01). CONLUSION: The renoprotective effect of valsartan on chronic experiment renal failure rats is similar as benazepril. valsartan and benazepril can improve glomerulosclerosis by decreasing the expression of TGF-β 1, FN and collagen IV in glomeruli.