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中国临床药理学与治疗学 ›› 2007, Vol. 12 ›› Issue (8): 896-899.

• 基础研究 • 上一篇    下一篇

罗格列酮逆转心力衰竭大鼠心脏间质纤维化的实验研究

刘洪智1,2, 高传玉1, 雷健3, 罗兵3, 李佐民3, 周军3, 贺立群3, 戚本玲2, 曹林生2   

  1. 1河南省人民医院心内科, 郑州 450000, 河南;
    2华中科技大学同济医学院附属协和医院心内科, 武汉 430022, 湖北;
    3武汉市第一医院心内科, 武汉 430022, 湖北
  • 收稿日期:2007-01-22 修回日期:2007-08-30 出版日期:2007-08-26 发布日期:2020-10-27
  • 作者简介:刘洪智,男,博士,主治医师,研究方向:心力衰竭及冠心病诊治。Tel:0371-65580756 E-mail:lhzhi@sina.com
  • 基金资助:
    武汉市科技计划项目(200302)

Experimental study on rosiglitazone reversing myocardial interstitial fibrosis of rats with heart failure

LIU Hong-zhi1,2, GAO Chuan-yu1, LEI Jian3, LUO Bing3, LI Zuo-min3, ZHOU Jun3,HE Li-qun3, QI Ben-ling2, CAO Lin-sheng2   

  1. 1Department of Cardiology, Henan Province Peoples Hospital, Zhengzhou 45000, Henan, China;
    2Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China;
    3Department of Cardiology, Wuhan First Hospital, Wuhan 430022, Hubei, China
  • Received:2007-01-22 Revised:2007-08-30 Online:2007-08-26 Published:2020-10-27

摘要: 目的: 研究过氧化酶体增殖物激活受体γ(PPARγ)配体罗格列酮能否逆转心力衰竭大鼠心脏间质纤维化。方法: 60 只雄性Wistar 大鼠分3 组:(1)心力衰竭模型组(CHF, n=25), 阿霉素2.5 mg/kg, 尾静脉注射, 每周1 次, 连续10 周;(2)心力衰竭模型+罗格列酮治疗组(ROS, n=25), ROS3 mg·kg-1·d-1, 灌胃治疗;(3)正常对照组(CON, n=10)。于实验第12 周, 进行超声检测评价其心功能, 用放免法检测血浆TNF-α、血管紧张素-II(Ang-Ⅱ)及醛固酮(Ald)水平, 氯胺T 法检测羟脯氨酸及胶原含量, 苦味酸天狼星红染色进行左室胶原特异染色及定量分析, 计算胶原容积分数(CVF), 并作HE 染色观察其组织学变化。结果: ROS 组较CHF组死亡率明显降低(20% vs 40%, P<0.01)。与CON 组相比,CHF 组血浆TNF-α、Ang-Ⅱ 及Ald 水平升高(P<0.01), 而ROS 治疗组较CHF 组降低(P<0.01)。CHF 组羟脯氨酸及胶原含量增加(P<0.01), 经ROS 治疗后有所减低。苦味酸天狼星红染色显示CHF 组左室胶原明显增加,CVF 明显增高(P<0.01);而ROS 组则纤维化明显减轻,CVF 降低(P<0.01)。病理学结果证实CHF 组符合心肌病样改变, 而ROS 组可逆转这种改变。结论: PPARγ配体罗格列酮通过抑制TNF-α、Ang-Ⅱ及Ald 等, 部分逆转心力衰竭大鼠心脏间质纤维化。

关键词: 过氧化酶体增殖物激活受体γ, 罗格列酮, 阿霉素, 心力衰竭, 间质纤维化

Abstract: AIM: To investigate whether the ligand of peroxisome Proliferator-activated receptor γ(PPARγ), rosiglitazone (ROS), can reverse myocardial interstitial fibrosis in rats with heart failure. METHODS: Sixty weight-matched adult male Wistar rats were randomly divided into 3 groups as follows:(1)the CHF group, in which 2.5 mg/kg of adriamycin (ADR)was weekly injected via a tail vein for 10 weeks (n=25);(2)the ROS group, concomitant ROS and ADR, in which ROS as a PPARγligand was administered by daily gavage at a dose of 3 mg·kg-1·d-1(n=25);(3)the control group (n=10).The cardiac function was evaluated by echocardiographic method.The plasma concentrations of TNF-α, Angiotensin II (Ang II)and Aldsterone (Ald)were determined by immunoradiometric assay at 12 weeks after treatment.The hydroxyproline and collagen content were determined by the methods of Chloramines T and Picric acid-Sirius red staining techniques.The pathological change was analyzed by histological hematoxylin-eosin staining. RESULTS: The mortality of ROS-treated rats was significantly lower than that of CHF group (20% versus 40%, P<0.01).The plasma concentrations of TNF-α, Ang II and Ald were higher in the CHF group than those in the control group (P<0.01), which was decreased by ROS treatment.The hydroxyproline and collagen content were increased in CHF group(both P<0.01), but decreased in ROS group.The myocardial collagen of left ventricle increased and the collagen volume fraction (CVF)increased significantly, which were partly reversed by ROS treatment(P<0.01).The pathological results showed there was changes of cardiomyopathy in CHF group, ROS reversed the pathological changes of left ventricular myocardium of CHF. CONCLUSION: Pretreatment with PPARγligand ROS could partly reverse myocardial interstitial fibrosis in rats with heart failure by downregulating the expression of TNF-α, Ang II and Ald.

Key words: peroxisome proliferator activated receptor γ, rosiglitazone, adriamycin, heart failure, interstitial fibrosis

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