依那普利对单侧输尿管梗阻大鼠肾组织胰岛素样生长因子-1表达及肾小管上皮细胞转分化的影响

Influence of Enalapil on expression of IGF-1 and tubular epithelium to mesenchyma transition in rats with unillateral ureter obstruction

目的观察血管紧张素转换酶抑制剂(ACEI)依那普利对单侧输尿管梗阻(UUO)大鼠肾组织胰岛素样生长因子-1(IGF-1)表达及肾小管上皮细胞转分化(EMT)的影响。方法采用UUO大鼠模型,雄性SD大鼠32只随机分为假手术组、模型组和依那普利组。依那普利组从造模前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。于造模后第14天处死大鼠,取梗阻侧肾组织,苏木精-伊红染色(HE)和Masson染色观察肾组织病理改变;实时定量逆转录-聚合酶链反应(RT-q PCR)检测肾组织IGF-1m RNA的表达;Western blot检测肾组织IGF-1、α-血管平滑肌肌动蛋白(α-SMA)和钙黏蛋白(E-cadherin)的表达。结果模型组大鼠肾间质损伤指数逐渐增加,肾间质胶原相对面积逐渐增大,IGF-1、α-SMA蛋白表达增加,IGF-1 m RNA和钙黏蛋白表达减少。经依那普利治疗后,肾间质损伤指数和肾间质胶原相对面积下降,IGF-1、α-SMA蛋白表达减少,IGF-1 m RNA和E-钙黏蛋白表达增加,与模型组比较,差异有统计学意义(P<0.05)。结论依那普利可通过抑制肾组织IGF-1表达抑制EMT,进而防治肾间质纤维化。

【Objective】 To investigate the effect of Enalapril on the expression of IGF-1 and epitheliumto-mesenchyma transition（EMT） induced by unilateral urethral obstruction（UUO） in rats. 【Methods】 UUO model was induced by ligating the left ureter in rats. Male Sprague-Dawley（SD） rats were randomly divided into sham-operated group, UUO model group and Enalapril-treated group. The rats were treated with Enalapril10 mg/（kg·d） by gastric gavage in the Enalapril-treated group and equivalent volume of normal saline in the sham-operated group and the model group. The rats were sacrificed on the 14 th day after UUO. Renal tissue pathological changes were observed by HE and Masson staining. The expression of IGF-1 m RNA was detected by real-time PCR, and the expressions of IGF-1, α-smooth muscle actin（α-SMA） and E-cadherin were detected by Western blot. 【Results】 There were obvious increases in renal interstitial damage index, relative collagen area and the expressions of IGF-1 and α-SMA, and decreases in the expressions of IGF-1 m RNA and E-cadherin protein in the renal tissues of the model group compared with the sham-operated group（P 〈0.05）. Enalapril significantly reduced the renal interstitial damage index and relative collagen area, inhibited the levels of IGF-1 and α-SMA, and increased the expressions of IGF-1 m RNA and E-cadherin protein in the Enalapril-treated group compared with the model group（P 〈0.05）. 【Conclusion】 Enalapril can attenuate renal interstitial fibrosis by suppressing the expression of IGF-1 and inhibiting the epithelium-to-mesenchyma transition.