延迟缺血预处理对急性心肌梗死大鼠梗死边缘区中小动脉再生及梗死面积的影响  

Delayed IPC exerts cardioprotective effect through neovascularization in a rodent permanent occlusive coronary rat model

作　　者：程劲松[1,2] 柯元南[2] 王慧[1,2] 吴文静[1,2] 孔炜[3] 郑金刚[2] 

机构地区：[1]北京协和医学院研究生院,北京100730 [2]中日友好医院心内科,北京100029 [3]北京大学医学部生理学教研室,北京100191

出　　处：《心脏杂志》2011年第1期1-6,共6页Chinese Heart Journal

基　　金：国家自然科学基金面上项目资金资助(30770865和30670849)

摘　　要：目的:探讨延迟缺血预处理(delayed ischemic preconditioning,DIPC)对急性心肌梗死(AMI)大鼠远期的心肌保护及其促进小动脉再生的作用。方法:将54只SD大鼠随机分为4组,即①缺血预处理(IPC)+AMI组:于IPC后24 h,结扎冠状动脉建立AMI大鼠模型(n=24);②AMI组:开胸后,只穿线不进行IPC,于24 h后结扎冠脉建立AMI大鼠模型(n=24);③IPC组:只进行IPC不结扎冠脉(n=3);④假手术组:开胸后,既不进行IPC操作也不结扎冠状动脉(n=3)。前两组于模型建立后3 d、7 d和14 d,用免疫组化染色法检测梗死边缘区毛细血管新生及小动脉再生;后两组分别于IPC后及假手术后24 h,用免疫组化染色法检测梗死边缘区毛细血管新生及血管内皮生长因子(VEGF)、血小板源生长因子-B(PDGF-B)表达。14 d后采用小动物超声检测心功能,Masson’s Trichrome染色法测量心肌梗死(MI)面积。结果:IPC组于IPC后24 h,缺血区的心肌中可见毛细血管新生,VEGF及PDGF-B表达明显增加(与假手术组相比,P<0.05)。与AMI相比,IPC+AMI组于建模后3 d、7 d和14 d,梗死边缘区心肌中毛细血管的密度和小动脉的密度均明显增加(P<0.05),MI面积减小(P<0.05),心功能改善(与AMI组相比,左室短轴缩短率增高,P<0.05)。结论:DIPC可减小MI的面积,改善心功能,这一作用与其增加梗死边缘区中的小动脉再生有关;缺血区心肌中VEGF及PDGF-B表达的增加可能是小动脉再生的刺激因素。AIM： To investigate whether delayed ischemic preconditioning（IPC） exerts a cardioprotective effect through arteriogenesis in a rodent permanent occlusive coronary rat model.METHODS： Fifty four rats were randomly divided into four groups.In IPC＋acute myocardial infarction（AMI） group（n=24）,rat left anterior descending coronary arteries were ligated 24 h after IPC.In AMI group（n=24）,rat left anterior descending coronary arteries were ligated without IPC.In IPC group（n=3）,rats were subjected to IPC procedure and in sham group（n=3）,rats were not subjected to either IPC or ligation.At 3,7,and 14 days,the heart sections of IPC＋AMI group and AMI group rats were obtained to detect the capillary density and arteriole density by immunostaining.Heart function and infarct size were measured by Masson’s trichrome staining and echocardiography in 14-day subgroup.At 24 h,the heart sections of IPC group and sham group were obtained to detect the capillary density and VEGF and PDGF-B expression.RESULTS： Neovascularization was seen in rat heart section 24 h after IPC.Compared with sham group,the expression of VEGF,PDGF-B in heart section in rats of IPC group increased significantly（P〈0.05）.Compared with those in AMI group,capillary density and arteriole density in heart sections in rats of IPC＋AMI group increased in 3-,7-and 14-day subgroups（P〈0.05）.Infarct size was reduced and heart function improved in 14-day subgroup（P〈0.05）.CONCLUSION： Delayed IPC reduces infarct size and improves heart function in a permanent occlusive rat model.This may result from increased functional arteriogenesis,whereas increased expression of VEGF,PDGF-B in heart section in rats of IPC group may contribute to proliferative arteriole.

关 键 词：延迟缺血预处理 急性心肌梗死 毛细血管新生 小动脉再生 大鼠 

分 类 号：R542.22[医药卫生—心血管疾病]