罗格列酮逆转心力衰竭大鼠心脏间质纤维化的实验研究  

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

作　　者：刘洪智[1] 高传玉[1] 雷健[2] 罗兵[2] 李佐民[2] 周军[2] 贺立群[2] 戚本玲[3] 曹林生[3] 

机构地区：[1]河南省人民医院心内科 [2]武汉市第一医院心内科 [3]华中科技大学同济医学院附属协和医院心内科

出　　处：《中国临床药理学与治疗学》2007年第8期896-899,共4页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：武汉市科技计划项目(200302)

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2.5mg/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),ROS3mg.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%vs40%,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。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 PPARγ ligand 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 Aidsterone （Aid） 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 Aid 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 PPARγ ligand ROS could partly reverse myocardial interstitial fibrosis in rats with heart failure by downregulating the expression of TNF-α, Ang Ⅱ and Aid.

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 

分 类 号：R965.2[医药卫生—药理学]