[依那普利对单侧输尿管梗阻大鼠转化生长因子-β1、结缔组织生长因子、Smad7及α-平滑肌肌动蛋白表达的动态观察]

[Dynamic observation of enalapril on the expression of TGF-beta1, CTGF, Smad7 and alpha-SMA in rats with unilateral ureteral obstruction].

作者信息

Wang Linna, Ning Wangbin, Tao Lijian, Wang Ling, Peng Zhangzhe

机构信息

Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410008, China.

出版信息

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2009 Mar;34(3):252-8.

PMID:19349682

Abstract

OBJECTIVE

To dynamically observe the effect of enalapril on the expression of transforming growth factor beta1 (TGF-beta1), connective tissue growth factor (CTGF), alpha-smooth muscle actin (alpha-SMA), and Smad7 in the obstructed kidney after unilateral ureteral obstruction (UUO) in rats, and to investigate the effect of enalapril on transdifferentiation of renal tubular epithelial cells.

METHODS

The model rats were induced by ligating the left ureter. Male Sprague-Dawley (SD) rats were divided into a normal control (sham-surgery) group, a model group, and a treatment group (enalapril 10 mg/ (kg * d) by gastric gavage from 24 h before the obstruction day). Rats were sacrificed on day 3, 7, 14, 21 after UUO was initiated. Sections of the renal tissue were stained with hematoxylin and eosin stain, which were used for histological and morphometric studies of the pathological change of the obstructed kidney. Real-time PCR was performed to examine the expression of TGF-beta1 mRNA and CTGF mRNA, and Western blot was performed to examine the expression of Smad7, alpha-SMA, and CTGF in the obstructed kidney.

RESULTS

The score of renal interstitial lesion increased with the extension of obstruction. The expression of TGF-beta1 mRNA, CTGF mRNA, alpha-SMA and CTGF increased in the model group with the extension of obstruction; but Smad7 expression decreased. Compared with the UUO group,the degree of renal interstitial lesion and the expression of TGF-beta1 mRNA, CTGF mRNA, alpha-SMA and CTGF were decreased, but the expression of Smad7 increased in the treatment group. Enalapril could significantly decrease TGF-beta1 mRNA on day 3, 7, 14, 21 after UUO. Enalapril could significantly affect the expression of CTGF mRNA,alpha-SMA,CTGF and Smad7 on day 3, 7, 14 after UUO initiation.

CONCLUSION

Enalapril significantly alleviates renal interstitial fibrosis by suppressing the expression of TGF-beta1, CTGF and alpha-SMA, upregulating the expression of Smad7, and has better effect at early stage (within 14 days after the UUO).

摘要

目的

动态观察依那普利对大鼠单侧输尿管梗阻（UUO）后梗阻肾组织中转化生长因子β1（TGF-β1）、结缔组织生长因子（CTGF）、α-平滑肌肌动蛋白（α-SMA）及Smad7表达的影响，探讨依那普利对肾小管上皮细胞转分化的作用。

方法

通过结扎左侧输尿管制备模型大鼠。将雄性Sprague-Dawley（SD）大鼠分为正常对照组（假手术组）、模型组和治疗组（从梗阻前24 h开始，每天经胃管给予依那普利10 mg/（kg·d））。在UUO术后第3、7、14、21天处死大鼠。取肾组织切片进行苏木精-伊红染色，用于观察梗阻肾组织病理变化的组织学和形态学研究。采用实时定量PCR检测梗阻肾组织中TGF-β1 mRNA和CTGF mRNA的表达，采用蛋白质免疫印迹法检测梗阻肾组织中Smad7、α-SMA及CTGF的表达。

结果

肾间质病变评分随梗阻时间延长而增加。模型组中，TGF-β1 mRNA、CTGF mRNA、α-SMA及CTGF的表达随梗阻时间延长而升高；而Smad7表达降低。与UUO组相比，治疗组肾间质病变程度及TGF-β1 mRNA、CTGF mRNA、α-SMA及CTGF的表达降低，但Smad7表达升高。依那普利可在UUO术后第3、7、14、21天显著降低TGF-β1 mRNA表达。依那普利可在UUO术后第3、7、14天显著影响CTGF mRNA、α-SMA、CTGF及Smad7的表达。