依那普利对大鼠肾间质纤维化时肾小管上皮细胞凋亡的影响
[Effect of enalapril on apoptosis of renal tubular epithelial cells in renal interstitial fibrosis in rats].
作者信息
Yang Hui, Zhang Weiru, Xie Tingting, Wang Xuan, Ning Wangbin
机构信息
Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha 410008, China.
出版信息
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2019 Jun 28;44(6):614-620. doi: 10.11817/j.issn.1672-7347.2019.06.002.
To observe the effect of enalapril on the apoptosis of renal tubular epithelial cells in renal interstitial fibrosis rats and to explore the mechanism of enalapril on renal interstitial fibrosis. Methods: Twenty-four SD male rats were randomly divided into a sham operation group, a model group and an enalapril group (n=8 in each group). The rats in the model group and the enalapril group underwent the operation of left urethral obstruction to establish the animal model of unilateral urethral obstruction (UUO). Fourteen days later after the operation, all rats were sacrificed and their obstructed kidneys were collected for HE and Masson staining to observe the pathological change of renal tissues. Terminal deoxynucleotidyl transferase-mediated (dUTP) nick end-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 Fas-associated death domain (FADD), apoptotic protease activating factor-1 (APAF-1) and C/EBP homologous protein (CHOP). Results: Compared with the sham operation group, the renal interstitial injury index and renal interstitial fibrosis index were significantly increased in the model group (P<0.05). Compared with the model group, the renal interstitial injury index and renal interstitial fibrosis index were both significantly decreased in the enalapril group (P<0.05). Compared with the sham group, the apoptosis rate of renal tubular epithelial cells was increased in the model group (P<0.05); compared with the model group, the apoptosis rate of renal tubular epithelial cells was significantly reduced in the enalapril group (P<0.05). The protein levels of FADD, APAF-1 and CHOP in the model group were significantly elevated than those in the sham group (all P<0.05), which were reversed in presence of enalapril (all P<0.05). Conclusion: Enalapril can alleviate renal interstitial fibrosis through inhibiting apoptosis of renal tubular epithelial cells in UUO rats.
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，并探讨依那普利治疗肾间质纤维化的作用机制。方法：将24只雄性SD大鼠随机分为假手术组、模型组和依那普利组（每组8只）。模型组和依那普利组大鼠行左侧输尿管梗阻手术，建立单侧输尿管梗阻（UUO）动物模型。术后14天，处死所有大鼠，取梗阻侧肾脏进行HE和Masson染色，观察肾组织病理变化。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）染色法检测肾小管上皮细胞凋亡情况。采用免疫组织化学和蛋白质印迹法检测Fas相关死亡结构域（FADD）、凋亡蛋白酶激活因子-1（APAF-1）和C/EBP同源蛋白（CHOP）的蛋白表达。结果：与假手术组比较，模型组肾间质损伤指数和肾间质纤维化指数显著升高（P<0.05）。与模型组比较，依那普利组肾间质损伤指数和肾间质纤维化指数均显著降低（P<0.05）。与假手术组比较，模型组肾小管上皮细胞凋亡率升高（P<0.05）；与模型组比较，依那普利组肾小管上皮细胞凋亡率显著降低（P<0.05）。模型组FADD、APAF-1和CHOP蛋白水平显著高于假手术组（均P<0.05），依那普利可使其逆转（均P<0.05）。结论：依那普利可通过抑制UUO大鼠肾小管上皮细胞凋亡减轻肾间质纤维化。
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