阿霉素心肌损伤大鼠模型的制备与评价  

Establishment and Evaluation of a Rat Model of Adriamycin-Induced Myocardial Injury

作　　者：苏丹[1] 刘鹏飞[1] 张柳[1] 宋伯根[2] 赵桂芬[2] 

机构地区：[1]同济大学医学院药理学教研室,上海200092 [2]同济大学医学院病理学教研室,上海200092

出　　处：《中国实验动物学报》2009年第6期442-444,I0002,共4页Acta Laboratorium Animalis Scientia Sinica

基　　金：上海市卫生局科研课题(No.2008047);同济大学医科发展基金(No.1509219027)

摘　　要：目的制备阿霉素心肌损伤大鼠模型,并对其进行评价。方法24只雄性SD大鼠随机分2组:正常对照组(CON,n=9)和阿霉素模型组(ADR,n=15)。ADR组腹腔注射阿霉素2 mg/kg,每周3次,连续2周,CON组注射相同体积的生理盐水,注射完毕后饲养5周;实验期间观察大鼠一般情况及死亡率;7周后检测心脏血流动力学及组织形态学变化,并进行心肌氧化损伤生化测定。结果ADR组大鼠死亡率为40%,CON组无死亡。与CON组比较,ADR组大鼠左室舒张末压(LVEDP)及左室内压最大下降速率(-LVdP/dtmax)显著升高(P<0.001,P<0.05);组织学检查结果符合心肌损伤病理学改变的典型特征;心肌丙二醛(MDA)含量明显增加(P<0.001);谷胱甘肽过氧化物酶(GSH-Px)活性显著降低(P<0.01)。结论按12 mg/kg的ADR总剂量,以每周3次,共两周,每次2mg/kg腹腔注射方式给药,7周后大鼠心脏产生明显功能及形态学异常,可成功建立ADR心肌损伤大鼠模型。Objective To establish and evaluate a rat model of adriamycininduced myocardial injury.Methods Tweenty-four male SD rats were randomly divided into two groups.The adriamycin（ADR） group（n=15） was injected intraperitoneally with six equal doses of ADR（2 mg/kg each time,with a cumulative dose of 12 mg/kg） over a period of two weeks,while the control group（n=9） received an equivalent volume of normal saline intraperitoneally alone.The Rats were observed for 5 weeks after treatment.The general conditions and mortality were recorded.At the end of experiment,the parameters of hemodynamics including LVSP,LVEDP,±LVdP/dtmax and HR were measured.The pathological changes were analyzed by histological hematoxylin-eosin staining.Glutathione peroxidase（GSH-Px） and superoxide dismutase（SOD） activity as well as malondialdehyde（MDA） content in heart tissue were measured according to the kit instructions,respectively.Results The cumulative mortality in the ADR group was 40%.Compared with the control group,LVEDP and-LVdP/dtmax were significantly increased in the ADR group（P〈0.001,P〈0.05）.The results of pathological examnation of the ADR group were consistent with characteristic changes of myocardial injury.Myocardial malondialdehyde（MDA） content was significantly increased and glutathione peroxidase（GSH-Px） activity decreased in the ADR group compared with those in the controls.Conclusion A rat model of adriamycin-induced myocardial injury has been successfully established by administration of ADR（cumulative dose,12 mg/kg） to rats in six equal intraperitoneal injections over a period of 2 weeks,resulting in cardiac dysfunction and histological damages.

关 键 词：阿霉素 心肌损伤 大鼠模型 

分 类 号：R-332[医药卫生]