苯那普利对单侧输尿管梗阻大鼠肾脏结缔组织生长因子表达的影响

目的探讨苯那普利对大鼠单侧输尿管梗阻(UUO)模型肾脏结缔组织生长因子(CTGF)表达的影响及其可能机制。方法24只SD大鼠随机分为假手术组、模型组和苯那普利组。建立大鼠UUO模型前1 d起,治疗组给予苯那普利10 mg/(kg.d)灌胃,假手术组及模型组以等量的蒸馏水灌胃。于术后第14天分别取术侧肾组织行HE、Mas-son染色及转化生长因子-β1(TGF-β1)、结缔组织生长因子(CTGF)、α-平滑肌肌动蛋白(-αSMA)和Ⅲ型胶原蛋白(ColⅢ)免疫组化染色,应用图像分析系统进行免疫组化半定量分析。结果苯那普利可以显著减轻肾间质损伤和肾间质纤维化程度(P<0.05),且可以显著抑制TGF-β1、CTGF、-αSMA及ColⅢ表达(P<0.05)。结论苯那普利可通过减少细胞外基质(ECM)产生细胞的活化、抑制TGF-β1的过度表达,从而降低CTGF表达,减少ECM的沉积,达到抗肾间质纤维化的作用。

Intervention of renal connective tissue growth factor expression and renal fibrosis by Benazepril: an experimental study in unilateral ureteral obstruction rats

Objective To study the effect of Benazepril on the renal connective tissue growth factor(CTGF) expression and interstitial fibrosis in unilateral ureteral obstruction(UUO) rats and to illuminate the possible mechanisms.Methods 24 Sprague-Dawley rats were randomly divided into Sham-operated,control and Benazepril groups.From the day before operation,the rats were under intragastric administration of Benazepril 10mg/(kg·d) in Benazepril group,and sodium chloride in tales doses in Sham and control groups.On the 14~(th) day after operation,the obstructed kidney was taken out to be measured by HE,Masson,and immunohistochemistry staining for TGF-β_1,CTGF,α-SMA and ColⅢ.Results The score of renal interstitial lesion and fibrosis index in Benazenpril were significantly lower than those in the control group(P<0.05);TGF-β_1,CTGF,α-SMA and ColⅢ in Benazepril group were significantly less than in the control group(P<0.05).Conclusion Benazepril may degrade renal interstitial fibrosis by decreaseing CTGF levels and deposition of ECM by way of reducing the activation of cell producing ECM and inhibiting the overexpression of TGF-β_1.