依那普利对肾间质纤维化大鼠模型的治疗作用研究

Therapeutic effect of enalapril on renal interstitial fibrosis in rats

目的构建单侧输尿管梗阻(UUO)大鼠模型,探讨依那普利对肾脏间质纤维化的抑制作用。方法 60只SD大鼠随机分为假手术组、模型组、低剂量[10 mg/(kg·d)]依那普利组(低剂量组)和高剂量[20 mg/(kg·d)]依那普利组(高剂量组),每组15只。HE、Masson染色观察肾组织病理变化和纤维化程度。Western blot检测蛋白表达。结果假手术组、模型组、低剂量组和高剂量组肾小管损伤评分分别为0.12±0.02、4.12±0.61、3.11±0.34、2.47±0.26,组间比较差异有统计学意义(P<0.01),其中低剂量组和高剂量组肾小管损伤评分显著低于模型组(P<0.01),高剂量组显著低于低剂量组(P<0.01)。假手术组、模型组、低剂量组和高剂量组肾间质纤维化评分分别为0.26±0.05、3.64±0.53、2.48±0.36、1.83±0.22,四组间比较差异有统计学意义(P<0.01),其中低剂量组和高剂量组肾间质纤维化评分显著低于模型组(P<0.01),且高剂量组低于低剂量组(P<0.01)。低剂量组和高剂量组P65、TGF-β1和Smad3蛋白相对灰度值低于模型组(P<0.01),且高剂量组低于低剂量组(P<0.01)。结论依那普利可以抑制NF-κB/TGF-β1/Smad3信号通路,抗肾间质纤维化。

Objective To establish UUO rats model and explore the inhibitory effect of enalapril on renal in-terstitial fibrosis.Methods Totally 60 SD rats were divided into sham-operated group(sham group,n=15),model group(n=15),low-dose[10 mg/(kg·d)]enalapril group(low-dose group,n=15)and high-dose[20 mg/(kg·d)]enalapril group(high-dose group,n=15).HE and Masson staining were used to observe the renal pathologi-cal change and degree of fibrosis.The protein expression was detected by Western blot analysis.Results Scores of re-nal tubular injury in sham group,model group,low-dose group,and high-dose group were 0.12±0.02,4.12±0.61,3.11±0.34,and 2.47±0.26,respectively,and there were significant differences among the four groups(P<0.01);the score in enalapril groups was lower than that in model group(P<0.01),and the score in high-dose group was lower than that in low-dose group(P<0.01).The score of renal interstitial fibrosis in sham group,model group,low-dose group,and high-dose group were 0.26±0.05,3.64±0.53,2.48±0.36,and 1.83±0.22,respectively,there be-ing significant differences among the four groups(P<0.01);the score in enalapril groups was lower than that in mod-el group(P<0.01),and the score in high-dose group was lower than that in low-dose group(P<0.01).The relative gray value of P65,TGF-β1 and Smad3 in enalapril groups was lower than that in model group(P<0.01),and the score in high-dose group was lower than that in low-dose group(P<0.01).Conclusion Enalapril can inhibit NF-κB/TGF-β1/Smad3 signaling pathway and play a role in managing renal interstitial fibrosis.