依那普利对大鼠肾间质纤维化中肾小管上皮细胞凋亡的作用

目的：观察依那普利对肾间质纤维化大鼠肾小管上皮细胞凋亡的影响，探讨依那普利抗肾间质纤维化的作用机制。方法：将24只SD雄性大鼠随机分为假手术组(n=8)、模型组(n=8)和依那普利治疗组(n=8)。对模型组和依那普利治疗组大鼠行左侧输尿管结扎术，建立单侧输尿管梗阻(unilateral urethral obstruction，UUO)模型。术后14 d处死大鼠，留取梗阻侧肾组织分别进行HE和Masson染色，观察各组大鼠肾组织病理改变，用脱氧核糖核苷酸末端转移酶介导的缺口末端标记法[terminal deoxynucleotidyl transferase-mediated (dUTP) nick end-labeling，TUNEL]染色检查肾小管上皮细胞凋亡，免疫组织化学及蛋白质印迹法检测Fas相关死亡结构域(Fas-associated death domain，FADD)、凋亡蛋白酶活化因子-1(apoptotic protease activating factor-1，APAF-1)、C/EBP同源蛋白(C/EBP homologous protein，CHOP)的蛋白表达。结果：HE染色、Masson染色显示模型组肾间质损伤指数、肾间质纤维化指数均较假手术组明显增高(均P<0.05)，依那普利治疗组肾间质损伤指数、肾间质纤维化指数均较模型组明显降低(均P<0.05)。TUNEL染色显示模型组肾小管上皮细胞凋亡计数较假手术组明显增多(P<0.05)，依那普利治疗组肾小管上皮细胞凋亡数较模型组明显减少(P<0.05)。免疫组织化学及蛋白质印迹法显示模型组肾组织FADD，APAF-1和CHOP的蛋白表达均较假手术组明显增多(均P<0.05)，依那普利治疗组肾组织FADD，APAF-1和CHOP的蛋白表达均较模型组明显降低(均P<0.05)。结论：依那普利可通过抑制UUO大鼠的肾小管上皮细胞凋亡而起到抑制肾间质纤维化的作用。

Effect of enalapril on apoptosis of renal tubular epithelial cells in renal interstitial fibrosis in rats

Objective: To observe the effect of enalapril on the apoptosis of renal tubular epithelial cells inrenal interstitial fi brosis rats and to explore the mechanism of enalapril on renal interstitial fi brosis.Methods: Twenty-four SD male rats were randomly divided into a sham operation group, amodel group and an enalapril group (n=8 in each group). The rats in the model group and theenalapril group underwent the operation of left urethral obstruction to establish the animal modelof unilateral urethral obstruction (UUO). Fourteen days later after the operation, all rats weresacrificed and their obstructed kidneys were collected for HE and Masson staining to observe thepathological change of renal tissues. Terminal deoxynucleotidyl transferase-mediated (dUTP) nickend-labeling (TUNEL) staining was used to detect the apoptosis of renal tubular epithelial cells.Immunohistochemistry and Western blotting were used to detect the protein expression of Fasassociateddeath domain (FADD), apoptotic protease activating factor-1 (APAF-1) and C/EBPhomologous protein (CHOP).Results: Compared with the sham operation group, the renal interstitial injury index and renalinterstitial fibrosis index were significantly increased in the model group (P<0.05). Comparedwith the model group, the renal interstitial injury index and renal interstitial fibrosis index wereboth significantly decreased in the enalapril group (P<0.05). Compared with the sham group, theapoptosis rate of renal tubular epithelial cells was increased in the model group (P<0.05); comparedwith the model group, the apoptosis rate of renal tubular epithelial cells was significantly reducedin the enalapril group (P<0.05). The protein levels of FADD, APAF-1 and CHOP in the modelgroup were significantly elevated than those in the sham group (all P<0.05), which were reversed inpresence of enalapril (all P<0.05).Conclusion: Enalapril can alleviate renal interstitial fibrosis through inhibiting apoptosis of renaltubular epithelial cells in UUO rats.