延迟缺血预处理介导的心肌保护与血管再生的关系  

Delayed ischemic preconditioning exert cardioprotective effect through neovascularization in a rodent permanent occlusive coronary rat model

作　　者：程劲松[1,2] 吴文静[1,2] 王慧[1,2] 杨鹏[2] 于长安[3] 温见燕[3] 廖文强[3] 潘琳[4] 柯元南[2] 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 [3]中日友好医院心血管病中心实验室 [4]中日友好临床医学研究所,北京100029

出　　处：《中日友好医院学报》2009年第6期353-356,F0004,共5页Journal of China-Japan Friendship Hospital

基　　金：国家自然科学基金资助;项目号30770865和30670849

摘　　要：目的:探讨延迟缺血预处理对急性心梗大鼠远期的心肌保护及其促进血管再生的作用。方法:分别制作4组大鼠模型。处理组:缺血预处理(IPC)后24h结扎冠脉建立急性心梗大鼠模型;对照组:开胸后只穿线未进行IPC,24h后结扎冠脉建立急性心梗大鼠模型;IPC组:只进行IPC不结扎冠脉;假手术组:既不进行IPC操作也不结扎冠脉。对前2组模型建立3d、7d和14d后免疫组化法检测梗死边缘区毛细血管新生、动脉再生。14d后评价心功能,测量心梗面积;对IPC组和假手术组采用免疫组化法检测缺血区心肌血管内皮生长因子(VEGF)表达。结果:处理组IPC后24h缺血区心肌可见到毛细血管新生,梗死3d、7d和14d后梗死边缘区心肌毛细血管密度和小动脉密度较对照组显著增加。处理组大鼠短轴缩短率较对照组显著升高,心梗面积减少。IPC组缺血区心肌VEGF表达较假手术组显著升高。结论:延迟缺血预处理改善心梗后远期心功能,减少心梗面积,增加梗死边缘区毛细血管新生和小动脉再生,至少部分与IPC后VEGF表达增加有关。Objective：To investigate whether delayed ischemic preconditioning（delayed IPC） exert cardioprotective effect through neovascularization in a rodent permanent occlusive coronary rat model.Methods：Four groups rats were investigated.In rats of treated group（T group）the left anterior descending coronary arteries were ligated after IPC procedure performed 24hrs which consists of four cycles 6 min ischemia separated by 6min reperfusion,rats of control group （C group） were ligated left anterior descending coronary arteries without IPC procedure and rats of IPC group（I group） were subjected to IPC procedure,rats of sham group（S group） were subjected to same procedure without IPC.On 3d,7d,14d, heart section of T group and C group rats were obtained to detect capillary density and arterial density by immunostaining.And left ventricular fractional shortening were evaluated by M-mode ultrasound,infarct size were measured by Masson＇s Trichrome staining in 14d sub-group.at 0hrs,6hrs,12hrs,24hrs,heart section of I group and S group were obtained to detect vascular endothelial growth factor（VEGF）expression so that we can know how effective IPC can exert on angiogenesis and arteriogenesis.Results：Neovascularization was found in rat heart section 24hrs after IPC procedure. Rats of T group have increased capillary density and arterial density in 3d,7d and 14d sub-group, reduced infarct size,improved FS in 14d sub-group compared with C group.VEGF expression in ischemie myocardium of IPC group rats was higher than S group rats.Conclusion：Delayed IPC improves heart function,reduces infarct size,increases capillary density and arterial density in a permanent occlusive rat model,at least partly involved in VEGF higher expression resulting from IPC.

关 键 词：延迟缺血预处理 心肌梗死 毛细血管新生 动脉再生 血管内皮生长因子 

分 类 号：R541.4[医药卫生—心血管疾病]