雷帕霉素降低炎症因子表达水平对小鼠心肌梗死的影响  

Rapamycin Improves Cardiac Function of Myocardial Infarction Mice by Reducing the Expression of Inflammatory Cytokines

作　　者：刘波[1] 陈澍[1] 杜心灵[1] 王宏飞[1] 李飞飞[1] 张安臣[1] 李冬寒[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院心血管外科,武汉430022

出　　处：《华中科技大学学报（医学版）》2013年第4期391-394,共4页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：教育部高等学校博士学科点专项科研基金资助项目(No.20110142110009)

摘　　要：目的观察雷帕霉素对小鼠心肌梗死心脏功能的保护作用并探讨可能的机制。方法 45只清洁级健康雄性昆明种小鼠随机分成假手术组(S组)、心肌梗死组(M组)及药物干预组(R组),每组各15只,术前1dR组注射雷帕霉素,S、M组注射等量生理盐水和无水乙醇。M组和R组呼吸机辅助开胸结扎左冠脉前降支(LAD),建立小鼠心肌梗死疾病模型,S组开胸缝线穿过LAD不结扎;术后R组腹腔注射雷帕霉素,S、M组注射等量生理盐水和无水乙醇对照。各组于术后第12天行心脏超声检查,检查各项心脏形态指标及心脏功能指标;第14天行苏木精-伊红(HE)染色病理检查及双抗体夹心酶联免疫吸附法(ELISA)检测心脏组织中炎症因子白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、巨噬细胞炎性蛋白1(MIP-1)的表达水平。结果超声心动图提示R组射血分数(EF)为(20.734±5.525)%、左室短轴缩短率(FS)为(10.774±4.468)%,均高于M组[EF(11.005±1.981)%,FS(5.486±0.899)%,P<0.01];心脏左心室壁厚度(Aws、Pws、Awd、Pwd)及收缩期、舒张期末心室内径(LV ESD、LV EDD)等形态指标均优于M组;ELISA检测结果提示R组炎症因子水平低于M组(P<0.05);HE病理检查提示R组炎症细胞浸润及胶原纤维增生程度均低于M组。术后2周,M组存活10只,R组存活11只,两组生存率经统计学分析,差异无统计学意义(P>0.05)。结论雷帕霉素对小鼠心肌梗死后的心脏功能具有一定的保护作用,其机制可能与其降低炎症因子水平,改善心室重塑有关,但对心肌梗死后小鼠的短期生存率无明显影响。Objective To examine the protective effect of rapamycin in mice with myocardial infarction and discuss the possible mechanism.Methods A total of 45Kunming mice were randomly divided into three groups：sham operation group（S group）,myocardial infarction group（M group）and drug intervention group（R group）.Myocardial infarction models were established in the M and R groups by ligating the left anterior descending coronary artery.After operation,rapamycin and equal amount of normal saline or ethanol were intraperitoneally injected into the mice in the R and M groups,respectively.Twelve days after operation,mice in all the groups were subjected to transthoracic echocardiography（TTE）to measure the myocardial morphology and function.At 14days,the enzyme linked sandwich immunoassay（ELISA）was used to measure the level of interleukin-1β（IL-1β）,interleukin-6（IL-6）,tumor necrosis factor-α（TNF-α）,and macrophage inflammatory protein 1（MIP-1）in the heart tissue;haematoxylin-eosin（HE）staining was employed to examine the pathological changes of myocardial tissues.Results The level of inflammatory cytokines was much lower in the R group than in the M group（P0.05）.TTE showed that the ejection fraction（EF）and the left ventricular fractional shortening were significantly higher in the R group than in the M group[（20.734±5.525）%vs.（11.005±1.981）%;（10.774±4.468）%vs.（5.486±0.899）%,P0.01].The left ventricular wall thickness（Aws,Pws,Awd and Pwd）,the left ventricular end-systolic diameter（LV ESD）and the left ventricular enddiastolic diameter（LV EDD）were significantly improved in the R group.ELISA revealed that the inflammatory factors were significantly decreased in the R group when compared with those in the M group（P0.05）.HE pathological examination showed that the inflammatory cells infiltration and the collagen fibers growth were improved in the R group.Two weeks after operation,there were 10and 11mice still alive in the M and R groups,respectively.

关 键 词：雷帕霉素 心肌梗死 炎症因子 心室重塑 

分 类 号：R542.2[医药卫生—心血管疾病]