依那普利对单侧输尿管梗阻大鼠肾间质纤维化的防治作用

Effect of enalapil on renal interstitial fibrosis in rats with unilateral ureteral obstruction

目的:动态观察血管紧张素转换酶抑制剂依那普利对单侧输尿管梗阻大鼠肾间质纤维化的影响。方法:采用单侧输尿管梗阻模型,雄性SD大鼠64只随机分为假手术组(n=16)、模型组(n=24)和依那普利治疗组(n=24)。治疗组从造模前24 h开始以依那普利10 mg/(kg.d)灌胃,模型组和假手术组以等体积的生理盐水灌胃。分别于造模后第3,7,14,21天处死大鼠,取梗阻侧肾组织,行HE染色和Masson染色观察各组大鼠肾组织病理改变,采用real-time PCR方法检测肾组织Ⅰ型胶原mRNA的表达,应用Western免疫印迹检测结缔组织生长因子(connective tissue growth factor,CTGF)蛋白表达。结果:随着梗阻时间的延长,模型组大鼠肾间质损伤指数评分逐渐增加,肾间质胶原相对面积逐渐增大,Ⅰ型胶原mRNA和CTGF蛋白表达逐渐增加。依那普利治疗后,肾间质损伤指数和肾间质胶原相对面积下降,Ⅰ型胶原mRNA和CTGF蛋白表达均减少,与模型组比较,差异在第3,7,14天有统计学意义(P<0.05),而在第21天无统计学意义(P>0.05)。结论:依那普利可减轻梗阻肾间质纤维化,这一作用可能与其能抑制肾组织Ⅰ型胶原mRNA和CTGF蛋白表达有关。

Objective To investigate the effect of enalapril on renal interstitial fibrosis in rats with unilateral ureteral obstruction （UUO）. Methods UUO model was induced by ligating the left ureter in rats. Male Sprague-Dawley （SD） rats were randomly divided into a sham-operated group （n=16）, a UUO model group（n =24）, and an enalapril treated group（n =24）. The rats were treated with 10 mg/kg · d by gastric gavage in the enalapril treated group from 24 h before the operation, and the rats were treated with the identical dose of normal saline in the other 2 groups. The rats were sacrificed at 3 , 7,14, and 21 days after UUO. Pathological changes of the renal tissue were observed by HE and Masson staining, the mRNA expression of collagen Ⅰ（ Col Ⅰ ） was detected by real-time PCR, and the protein expression of connective tissue growth factor （CTGF） was detected by Western blot. Results The renal interstitial damage index, relative collagen area and the expression of Col ⅠmRNA and CTGF in the renal tissues in the model group increased with the prolongation of obstruction. Enalapril significantly reduced the renal interstitial damage index and relative collagen area, and inhibted the expression of Col Ⅰ mRNA and CTGF. There was significant difference on day3,7,and 14 （P〈0.05）, but not on day 21 （P〉0.05）.Conclusion Enalapril significantly attenuates renal interstitial fibrosis by supressing the expression of Col Ⅰ mRNA and CTGF.