罗格列酮对高血压大鼠肾保护作用的研究

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (3): 269-273.

罗格列酮对高血压大鼠肾保护作用的研究

杜密稳, 黄红春, 刘淑华, 闫晗, 张丽丽, 朱刚艳, 赵志明, 汪福良, 李莉

武汉大学人民医院老年病科, 武汉430060, 湖北

收稿日期:2008-12-09 修回日期:2008-12-09 发布日期:2020-10-27
通讯作者: 刘淑华,女, 主任医师, 副教授, 硕士生导师, 研究方向:高血压肾损害。Tel:13971222028 E-mail:liushuhua200866@163.com
作者简介:杜密稳, 女, 硕士研究生, 研究方向:老年多器官疾病及COPD 的基础与临床研究。Tel:13437179869 E-mail:miwendu @sohu.com
基金资助:
湖北省科技攻关项目(2007AA301B35-4)

Renal protective effect of rosiglitazone in hypertensive rats

DUMi-wen, HUANG Hong-chun, LIU Shu-hua, YAN Han, ZHANG Li-li, ZHU Gang-yan, ZHAO Zhiming, WANG Fu-liang, LI Li

Department of Geriatric, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, China

Received:2008-12-09 Revised:2008-12-09 Published:2020-10-27

摘要/Abstract

摘要： 目的观察结缔组织生长因子(CTGF) 在两肾一夹高血压大鼠肾间质中的表达及其与肾损害的关系, 探讨罗格列酮对CTGF 在肾间质表达的影响及高血压肾保护作用的机制。方法两肾一夹高血压大鼠随机分为阳性对照组(B 组) 、罗格列酮治疗组(C 组), 假手术组作为阴性对照组(A组)。监测各组大鼠各阶段血压的变化, 检测尿β2微球蛋白(β2-MG) 、尿素氮(Bun) 、血肌酐(Cr)。免疫组化法检测CTGF 在肾组织中的表达, 并判断肾组织的病理学变化及肾间质纤维化程度。结果治疗前B 组与C 组的尿β2-MG 均较A 组明显升高(P<0.01), B 组与C 组之间的差异无统计学意义(P >0.05), 而治疗后C 组的尿β2-MG 较B组明显降低(P<0.05) ;CTGF 在B 组和C 组的表达较A 组均明显增加(P<0.01), 而C 组CTGF 的表达较B 组降低(P<0.05)。CTGF 的表达与β2-MG 及肾间质纤维化呈正相关(r =0.734, P<0.01 ;r =0.777, P<0.01)。结论罗格列酮可以降低血压, 减少蛋白尿, 下调CTGF 在肾间质的表达, 从而延缓肾间质纤维化(RIF) 的发展, 发挥肾保护作用。

关键词: 两肾一夹高血压大鼠, 罗格列酮, 肾间质纤维化, 结缔组织生长因子

Abstract: AIM: To observe the expression of connective tissue growth factor(CTGF) in renal interstitium of two-kidney one-clip hypertensive rats and the relationship between CTGF and renal damage, and to investigate the influnece of rosiglitazone on the expression of CTGF in renal interstitium and the mechanisms of renal protection of rosiglitation. METHODS: Twokidney one-clip hypertensive rats were divided randomly into the positive control group(group B) and the rosiglitazone therapy group(group C), sham operated group were fed as the negative control group(group A).The changes of blood pressure were monitored in each stage of experiment of all groups.The urine β2-MG, blood urea nitrogen (Bun) and serum creatinine (Cr) were detected, the expression of CTGF in the nephridial tissue was detected by immunohistochemistry, the pathological changes and the degree of renal interstitial fibrosis respectively were judged. RESULTS: Compared with group A the contents of β2-MG were markedly increased in group B and C(P<0.01) before the treatment, there was no significant difference between group B and C (P >0.05).Compared with group B, the contents of β2-MG in group C were decreased significantly(P<0.05) after the treatment.The expressions of CTGF in group B and C were significantly increased compared with A (P<0.01), the expressions of CTGF were decreased in group C (P<0.05) compared with group B.There was a significant positive correlation between the expressions of CTGF, the contents of β2-MG and the scores of renal interstitium fibrosis (r = 0.734, P<0.01 ;r =0.777, P<0.01). CONCLUSION: Rosiglitazone can delay the development of renal interstitial fibrosis by reducing blood pressure and albuminuria, and downregulating the expressions of CTGF in renal interstism so it educes kidney protection.

Key words: two-kidney one-clip hypertensive rats, rosiglitazone, renal interstitial fibrosis, connective tissue growth factor

中图分类号:

R544.1

杜密稳, 黄红春, 刘淑华, 闫晗, 张丽丽, 朱刚艳, 赵志明, 汪福良, 李莉. 罗格列酮对高血压大鼠肾保护作用的研究[J]. 中国临床药理学与治疗学, 2009, 14(3): 269-273.

DUMi-wen, HUANG Hong-chun, LIU Shu-hua, YAN Han, ZHANG Li-li, ZHU Gang-yan, ZHAO Zhiming, WANG Fu-liang, LI Li. Renal protective effect of rosiglitazone in hypertensive rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(3): 269-273.

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