依那普利在大鼠单侧输尿管梗阻再通模型中的抗纤维化作用

Enalapril suppresses renal fibrosis after release of unilateral ureteral obstruction in rats

目的:探讨依那普利对大鼠单侧输尿管梗阻再通模型肾脏纤维化的影响。方法:18只SD大鼠随机分为两组:假手术组(6只)以及单侧输尿管梗阻模型组(12只)。输尿管梗阻3天后,实施梗阻再通手术,再将大鼠随机分为模型组(6只)以及依那普利组(6只),术后,依那普利组给予依那普利灌胃10mg/kg/d,假手术组以及模型组给予等量0.5%CM-CNa溶液灌胃。用药2周后,取术侧肾组织做HE染色,并采用Raford评分系统对肾间质损伤程度进行评分;用Real-timePCR方法检测I、III型胶原以及CT-GFmRNA的表达;用Westernblot方法检测CTGF蛋白水平的表达。结果:模型组大鼠肾脏损伤程度,I、III型胶原mRNA表达水平,以及CTGFmRNA和蛋白表达水平均比假手术组明显上升(P<0.01)。经依那普利治疗后,与模型组相比,以上指标均显著下降(P<0.01)。结论:依那普利能有效阻止大鼠单侧输尿管梗阻再通后肾脏纤维化的进展。依那普利抗纤维化的作用机制可能与抑制CTGF的表达有关。

Objective： To investigate the effects of Enalapril （E） on renal fibrosis of rat release of unilateral ureteral obstruction （RUUO） model. Methods： Rats were randomly divided into 2 groups： （1） Sham group （n=6）; （2） unilateral ureteral obstruction （UUO） group （n=12）. Three days after induction of UUO, release the obstruction, then the rats in UUO group were divided into the following groups： （1） Release group as model control （n=6）; （2） Release of UUO treated with Enalapril （10mg/kg/d, intragastric administration, n=6）. Both the sham group and model control were intragastricly administrated with 0.5% CM-CNa. Two weeks after administration, the renal interstitial injury scores, collagen Ⅰ, collagen Ⅲ and CTGF were assessed and compared. Result： The renal interstitial injury scores, mRNA expression level of collagen Ⅰ and collagen Ⅲ, protein and mRNA expression level of CTGF were increased in RUUO model compared with sham group （P〈0.01） and reduced in Enalapril treated group compared with RUUO model control group （P〈0.01）. Conelusions： Enalapril can obviously reduce renal tubulointerstital fibrosis after release of unilateral ureteral obstruction in rats. The mechanism of Enalapril may be involved with the reduction of CTGF.