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目的 :探讨肾小球硬化大鼠肾组织转化生长因子 β1(TGF - β1)基因及蛋白表达 ,以及苯那普利和芦沙坦的影响及其意义。方法 :大鼠随机分成假手术组 (C组 ) ,肾小球硬化组 (D组 ) ,肾小球硬化苯那普利治疗组 (DB组 )和肾小球硬化芦沙坦治疗组 (DL组 ) ,治疗 6周后用RT -PCR检测肾皮质转化生长因子 β1(TGF - β1)mRNA和Ⅳ型胶原 (ColⅣ )mRNA表达 ,WesternBlotting检测TGF - β1蛋白表达 ,免疫组化测定肾组织ColⅣ ,并观察病理及生化改变。结果 :肾小球硬化组出现明显蛋白尿 ,血白蛋白下降及胆固醇上升 ,与假手术组比较有统计学差异 (P <0 .0 5或P <0 .0 1) ,肾小球系膜细胞增生 ,细胞外基质沉积 ,肾皮质TGF - β1mRNA和蛋白表达分别比假手术组增加 3.5 9倍和 2 .6 0倍 ,ColⅣmRNA和蛋白表达分别比假手术组升高 2 .5 7倍和 1.4 0倍。苯那普利和芦沙坦分别治疗 6周后 ,能明显减轻肾病生化改变及病理改变 ,肾皮质TGF - β1mRNA和蛋白表达分别下调 4 6 %、5 3%和 5 5 %、5 9% ,ColⅣmRNA和蛋白表达分别下降 4 6 %、5 4 %和 4 3%、4 8%。结论 :苯那普利和芦沙坦通过下调TGF - β1mRNA和蛋白的表达 ,减少肾小球细胞外基质的沉积 ,延缓肾小球硬化。
Objective: To investigate the expression of transforming growth factor β1 (TGF - β1) gene and its protein in renal tissue of rats with glomerulosclerosis and the effects of benazepril and losartan on it. Methods: The rats were randomly divided into sham operation group (C group), glomerulosclerosis group (D group), glomerulosclerosis benazepril treatment group (DB group) and glomerulosclerosis losartan treatment group (DL The expression of transforming growth factor β1 (TGF - β1) mRNA and collagen Ⅳ mRNA in renal cortex were detected by RT - PCR after 6 weeks of treatment. The expression of TGF - β1 protein was detected by Western Blotting. The expressions of Col Ⅳ, And observe the pathological and biochemical changes. Results: Significant proteinuria, decreased serum albumin and increased cholesterol were found in glomerulosclerosis group, which were significantly different from those in sham operation group (P <0.05 or P <0.01), glomerular mesangial Cell proliferation, extracellular matrix deposition, renal cortex TGF - β1 mRNA and protein expression were 3.59 times and 2.6 times higher than the sham operation group, Col Ⅳ mRNA and protein expression were increased 2.57 times and 1.4 0 times. After benazepril and losartan treatment for 6 weeks, the renal biochemical changes and pathological changes were significantly alleviated. The expressions of TGF - β1 mRNA and protein in renal cortex were decreased by 46%, 53%, 55%, 59% And protein expression decreased by 46%, 54% and 43%, 48% respectively. Conclusion: Benazepril and losartan can reduce glomerular extracellular matrix deposition and delay glomerulosclerosis by down - regulating the expression of TGF - β1 mRNA and protein.