依那普利对大鼠早期肾间质纤维化的影响

Effect of enalapril on early stage of renal interstitial fibrosis in rats

目的:观察依那普利对早期肾间质纤维化形成大鼠的疗效,并探讨其作用机制。方法:将60只雄性SD大鼠随机分为假手术组、单侧输尿管梗阻模型组和依那普利治疗组(每组20只),治疗组于手术后第4天开始以依那普利灌胃,术后第14天取各组大鼠肾组织分别行HE染色和Masson染色,免疫组织化学检测Ⅰ型胶原、III型胶原在肾组织的蛋白表达。应用Real-time PCR方法检测肾组织中Ⅰ型胶原、III型胶原、血小板源生长因子(platelet drived growth factor,PDGF)-B、转化生长因子(transforming growth factor,TGF)-β1、结缔组织生长因子(cen-nective tissue growth factor,CTGF)mRNA的水平。应用Western免疫印迹方法检测PDGF-B蛋白的表达。结果:依那普利治疗组大鼠肾脏的肾间质损伤指数、肾间质胶原评分、Ⅰ型胶原、Ⅲ型胶原,以及细胞因子PDGF-B,TGF-β1,CTGF的表达均比模型组明显下降(均P<0.05)。结论:依那普利可通过下调细胞因子PDGF-B,TGF-β1,CTGF的表达而起到治疗单侧输尿管梗阻大鼠肾间质纤维化的作用。

Objective To investigate the effects of enalapril on the early stage of renal interstitial fibrosis in rats and the underlying mechanism. Methods Sixty male Sprague -Dawley rats were randomly divided into 3 groups： a sham-operated group, a unilateral ureteral obstruction （UUO） model group and a enalapril treated group （n = 20 in each group）. For the enalapril group, rats received enalapril by gastric gavage from Day 4 after UUO. All rats from each group were killed on Day 14 after surgery. Renal tissue were observed by HE and Masson staining, the mRNA expression of collagen Ⅰ, collagen Ⅲ, platelet derived growth factor （PDGF）-B, transforming growth factor （TGF）-β1, connective tissue growth factor （CTGF） were detected by Real-time PCR, and the protein expressions of collagen Ⅰ and Ⅲ or PDGF-B was examined by immunohistochemical assay or Western blot. Results The renal tubulointerstitial injury able to attenuate the tubulointerstitial fibrosis in UUO rats by decreasing the expression of cytokines including PDGF-B, TGF-β1 and CTGF.