依那普利对大鼠肾间质纤维化中TGF-β1,p-Smad2/3及Smad7的作用

Effect of enalapril on the expression of TGF-β1,p-Smad2/3 and Smad7 in renal interstitial fibrosis in rats

目的:观察依那普利对肾间质纤维化大鼠肾组织中TGF-β1,p-Smad2/3及Smad7的影响,探讨依那普利抗肾间质纤维化的作用机制。方法:将30只雌性SD大鼠随机分为假手术组、模型组和依那普利治疗组。对治疗组和模型组大鼠行左侧输尿管结扎术建立单侧输尿管梗阻的动物模型。术后14d处死大鼠,留取梗阻侧肾组织行HE和Masson染色以观察各组大鼠肾组织病理改变,用免疫组织化学方法检测ColⅠ,TGF-β1,p-Smad2/3和Smad7的蛋白水平表达,用RT-PCR方法检测TGF-β1和Smad7mRNA水平表达。结果:模型组肾间质损伤指数、胶原相对面积及间质内ColⅠ表达均较假手术组增高(P<0.01),依那普利治疗后好转。假手术组肾组织TGF-β1蛋白及mRNA表达、p-Smad2/3蛋白表达较低,模型组表达明显增强(P<0.01),依那普利治疗后明显减弱(P<0.01)。假手术组肾组织可见较多的Smad7蛋白及mRNA表达,模型组肾组织Smad7表达明显减弱(P<0.01),依那普利治疗后Smad7表达较模型组增强(P<0.01)。结论:依那普利可以通过影响单侧输尿管梗阻大鼠肾组织中TGF-β/Smads信号通路中的TGF-β1,p-Smad2/3和Smad7而起到抑制纤维化的作用。

Objective To explore the mechanism of enalapril for renal interstitial fibrosis by observing the effect of enalapril on the expression of transforming growth factor-β1 （ TGF-β1 ） , p- Smad2/3 and Smad7 in renal tissuess of unilateral urethral obstruction （ UUO ） rat model. Methods Thirty female Sprague-Dawley （SD） rats were randomly subdivided into a sham-operated group, a model group and an enalapril treated group. UUO model was induced by ligating the left ureter of rats. All rats were sacrificed 14 days after UUO. Pathological changes of the renal tissue were observed by HE and Masson staining, the protein expressions of Collagen Ⅰ（Col Ⅰ） , TGF-β1, p- Smad2/3 and Smad7 were detected by immunohistoehemical staining, and the mRNA expressions of TGF-β1 and Smad7 were detected by RT-PCR. Results The renal interstitial damage index, the relative Collagen area and the expression of Col Ⅰ in the model group significantly increased （P 〈 0.01 ）. Enalapril reduced these indexes. The protein and mRNA expressions of TGF-β1 and the protein expressions of p-Smad2/3 were low in the sham-operated group, but were strongly positive in the model group, and enalapril could decrease the expressions of TGF-β1 and p-Smad2/3 （ P 〈 0.01 ）. The protein and mRNA expressions of Smad7 in the model group were less than that in the sham-operated group （ P 〈 0.01 ） , and enalapril could improve the expressions of Smad7 （ P 〈 0.01 ）. Conclusion Enalapril could inhibit the renal interstitial fibrosis by affecting TGF-β1, p-Smad2/3 and Smad7 of TGF-β/smads pathway in the renal tissues of UUO rats.