过氧化物酶体增殖物激活受体γ在阿霉素致心力衰竭大鼠左室心肌中表达与罗格列酮的干预作用  

Expression of peroxisome proliferator activated receptor gamma in left ventricular myocardium with adriamycin-induced congestive heart failure and the interventional effect of rosiglitazone

作　　者：雷健[1] 狄鸣[1] 李佐民[1] 昌薇[1] 田立群[1] 刘洪智[2] 曹林生[2] 

机构地区：[1]武汉市第一医院心内科,湖北省武汉市430022 [2]华中科技大学同济医学院附属协和医院心内科,湖北省武汉市430022

出　　处：《中国组织工程研究与临床康复》2007年第51期10260-10264,共5页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：武汉市科技计划项目资金资助(200302)~~

摘　　要：目的:研究表明,过氧化物酶体增殖物激活受体γ配体可保护心脏减轻缺血再灌注损伤,降低心肌梗死面积,促进缺血再灌注后心功能的恢复。观察过氧化物酶体增殖物激活受体γ对实验性心力衰竭的保护作用。方法:实验于2003-11/2004-07在华中科技大学同济医学院完成。①实验分组:成年雄性Wistar大鼠60只,体质量(265±43)g,随机抽签法分为心衰模型组(n=25),治疗组(n=25)和正常对照组(n=10)。②实验方法:建立阿霉素致心力衰竭大鼠模型,心衰模型组:尾静脉注射阿霉素2.5mg/kg,1次/周,连续10周;治疗组:在首次注射阿霉素前两周开始给予罗格列酮3mg/(kg·d)灌胃治疗,一直持续到第12周;正常对照组:用相同容量的生理盐水代替阿霉素,给药方法同心衰模型组。③实验评估:所有大鼠分别于第12周进行超声和血流动力学及血浆生化指标的检测;苦味酸天狼星红染色后显微镜下观察心肌组织,并应用HMIAS-2000自动图像分析系统测量组织切片的胶原容积分数;反转录-聚合酶链反应检测过氧化物酶体增殖物激活受体γ的mRNA表达;苏木精-伊红染色后显微镜下定性观察形态学改变。结果:纳入大鼠60只,心衰模型组大鼠12周累计死亡10只,死亡原因主要为充血性心力衰竭,生存率为60%,治疗组大鼠生存率为80%(P<0.01),而正常对照组全部存活。①反转录-聚合酶链反应检测结果显示,心衰模型组左室心肌中过氧化物酶体增殖物激活受体γ的mRNA表达较正常对照组降低(P<0.01),治疗组过氧化物酶体增殖物激活受体γ的mRNA表达高于心衰模型组,而低于正常对照组(P<0.01)。②治疗组较心衰模型组相比,心功能各项指标改善;血浆肿瘤坏死因子α、血管紧张素Ⅱ及醛固酮水平降低(P<0.01)。③苦味酸天狼星红染色显示心衰模型组左室胶原增多,心肌间质明显纤维化。与正常对照组比较,心衰模型组胶原容积分数增加,差异�AIM: Recent studies have shown that peroxisome proliferator activated receptor γ (PPARγ) ligand could prevent heart from ischemia/reperfusion injury, decrease myocardial infarction area and promote the recovery of heart function after ischemia/reperfusion. In this study, the protective effect of PPARγ on clinical heart failure (CHF) was investigated. . METHODS: The experiment was performed in the Tongji Medical College, Huazhong University of Science and Technology from November 2003 to July 2004. ①Sixty adult male Wistar rats of (265±43) g were randomly divided into CHF group (n =25), treatment group (n =25) and control group (n =10). ②CHF models were established by adriamycin. In CHF group, 2.5 mg/kg adriamycin was injected through vena caudalis, once a week for 10 weeks; in treatment group, rosiglitazone (3 mg/kg·d) was infused at 2 weeks before the first injection of adriamycin until the 12th week; in control group, the same volume normal saline was injected with the same method as CHF group. ③Hemodynamics and echocardiographic measurements were obtained at the 12th week after treatment. The myocardium was observed after picrosirius-polarization method staining, and the collagen volume fraction (CVF) was investigated using HMIAS-2000 automatic imaging analysis system; The expression of PPARγ mRNA was measured by RT-PCR, and morphological changes were observed after HE staining. RESULTS: Sixty rats were enrolled, and 10 in CHF group died of congestive heart failure during the 12 weeks with the survival rate of 60%; while in treatment group was 80% (P < 0.01), and no death was found in control group. ①RT-PCR detection showed that the expression of PPARγ mRNA in left ventricular myocardium was significantly decreased in CHF group compared to control group (P < 0.01); the expression in treatment group was higher than CHF group but lower than control group (P < 0.01). ②Compared with CHF group, the heart function indexes in treatment group were markedly improved; The plasma concentrations of tumor

关 键 词：过氧化物酶体增殖物激活受体Γ 配体 罗格列酮 阿霉素 心力衰竭 

分 类 号：R542.2[医药卫生—心血管疾病]