苯那普利干预Wnt信号通路抑制UUO大鼠肾纤维化的实验研究

中国临床药理学与治疗学 ›› 2017, Vol. 22 ›› Issue (12): 1332-1339.

苯那普利干预Wnt信号通路抑制UUO大鼠肾纤维化的实验研究

赵燕云¹，吴小燕^2,3，汪国敏^2,3，冯雨林^2,3，董飞侠^3,4

¹浙江中医药大学附属温州中医院药剂科，温州 325000，浙江； ²浙江中医药大学，杭州 310000，浙江；³浙江中医药大学附属温州中医院大士门院区肾内科，温州 325000，浙江；⁴温州老年病医院肾内科，温州 325000，浙江

收稿日期:2017-04-24 修回日期:2017-05-15 出版日期:2017-12-26 发布日期:2018-01-02
通讯作者: 董飞侠，男，博士，主任中医师，教授，硕士生导师，主要从事肾纤维化药理研究。 Tel: 18058365536 E-mail:cgrsfhtd@163.com
作者简介:赵燕云，女，本科，副主任药师，主要从事抗肾纤维化药理研究。 Tel: 18058365536 E-mail:zhaoyy88988@163.com
基金资助:
浙江省自然科学基金（LY14H270001）；浙江省151人才专项；温州市551人才专项；温州市高层次人才课题资助；浙江省中医药管理局课题资助（2013ZB121）

Experimental study of benazepril intervene Wnt signaling inhibits renal fibrosis in UUO rats

ZHAO Yanyun ¹, WU Xiaoyan^2,3, WANG Guomin ^2,3, FENG Yulin ^2,3, DONG Feixia^3,4

¹ Department of Pharmacy, Wenzhou Hospital of Traditional Chinese Medicine, Wenzhou 325000, Zhejiang, China; ²Zhejiang University of Traditional Chinese Medicine, Hangzhou 310000, Zhejiang, China; ³ Department of Nephrology, Wenzhou Hospital of Traditional Chinese Medicine, Wenzhou 325000, Zhejiang, China; ⁴Department of Nephrology, Wenzhou Geriatric Hospital, Wenzhou 325000, Zhejiang, China

Received:2017-04-24 Revised:2017-05-15 Online:2017-12-26 Published:2018-01-02

摘要/Abstract

摘要：

目的: 探讨苯那普利对肾纤维化的拮抗作用。方法: 将54只SD大鼠随机分为3组：假手术组、模型组、苯那普利组，除假手术组外，其他各组均采用单侧输尿管结扎手术方法建立大鼠肾纤维化模型，取手术侧肾组织做病理检测，Masson染色观察其病理变化，冰冻切片免疫荧光染色检测转化生长因子-β1（TGF-β1）、IV 型胶原蛋白（Col-IV）、 Wnt1、Wnt4在肾组织的阳性染色表达。实时荧光定量 PCR检测TGF-β1、Col-IV、Wnt1、Wnt4的mRNA 在肾组织中的表达情况。结果: Masson染色显示：与假手术组比较，各造模组胶原纤维蓝染部分明显增多、肾纤维化程度显著增加；与模型组比较，苯那普利组胶原纤维蓝染部分明显减少、肾纤维化程度相对减少。免疫组化和PCR结果显示：与模型组相比，苯那普利组Wnt1、Wnt4、TGF-β1、Col-IV阳性表达及mRNA表达显著下降。结论: 苯那普利能通过降低TGF-β1、Col-IV、Wnt1、Wnt4的表达，有效降低肾纤维化水平，从而达到改善肾纤维化的作用。

关键词: 苯那普利, 肾纤维化, 单侧输尿管结扎, Wnt信号通路

Abstract:

AIM: To investigate the antagonism mechanism of benazepril on renal fibrosis of unilateral uretreal obstructire(UUO). METHODS: Fifty-four Sprague-Dawley (SD) rats were randomly divided into three groups: sham operation group, model group, benazepril group. All the other groups were treated with surgery method of unilateral ureteral ligation to establish a rat model of renal fibrosis except the sham operation group. The pathological changes were observed by Masson staining; the positive staining expression of TGF-beta1, Col-IV, Wnt1, Wnt4 in frozen sections were observed by immunofluorescence staining; the expressions TGF-beta1, Col-IV, Wnt1and Wnt4 mRNA in renal tissues were detected by real time fluorescence quantitative PCR. RESULTS: Masson staining results: compared with the sham group, the parts of blue dye collagen fiber and the degree of renal fibrosis increased significantly in all modeled groups; compared with the model group, the parts of blue dye collagen fiber and the degree of renal fibrosis decreased significantly in benazepril group. Immunofluorescence and PCR results: compared with the model group, the positive expression of Wnt1, Wnt4, TGF-beta1, Col - IV and mRNA in the benazepril group decreased significantly. CONCLUSION: Benazepril can improve renal fibrosis by inhibiting the expression of TGF-beta1, Col-V, Wnt1, Wnt4 and ameliorating the level of renal fibrosis.

Key words: benazepril, renal interstitial fibrosis, unilateral ureteral obstruction, Wnt signaling

中图分类号:

R965.2

赵燕云，吴小燕，汪国敏，冯雨林，董飞侠. 苯那普利干预Wnt信号通路抑制UUO大鼠肾纤维化的实验研究[J]. 中国临床药理学与治疗学, 2017, 22(12): 1332-1339.

ZHAO Yanyun, WU Xiaoyan, WANG Guomin, FENG Yulin, DONG Feixia. Experimental study of benazepril intervene Wnt signaling inhibits renal fibrosis in UUO rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(12): 1332-1339.

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