大鼠心包膜组织对其缺血心肌的保护和再生作用  

Protective role of pericardial tissue on injured myocardium in rats

作　　者：王晓明[1] 许林海[1] 孙高忠[1] 孟群[2] 

机构地区：[1]浙江省人民医院心胸外科,杭州310014 [2]浙江省人民医院病理科,杭州310014

出　　处：《中华医学杂志》2011年第42期3012-3015,共4页National Medical Journal of China

基　　金：浙江省科技计划（2010C33137）

摘　　要：目的研究心包膜组织中是否有干细胞现象，能否对梗死后的心肌起到保护和修复作用。方法结扎Wistar大鼠冠状动脉左前降支（LAD）制作心肌梗死（简称心梗）模型。术中分别保留完整心包组织（＋PC组，n=8）和去除心包组织（-PC组，n=10）。心梗7d以后用超声心动图分析大鼠的心功能恢复情况；2，3，5．氯化三苯基四氮唑（ITC）染色测定梗死区的成活心肌组织；溴脱氧尿苷（BrdU）掺人实验检测新生的心肌细胞；免疫组化检测心包膜组织中心脏干细胞特征蛋白的免疫表象（SCA-1，c-kit和KDR）。结果超声心动图分析结果显示，＋PC组左室射血分数、左室短轴缩短率均高于-PC组（52±12比37±12，36±14比25±13，均P〈0．05）。TTC染色发现，心包组的再生心肌组织明显多于无心包组，这些细胞〉90％为BrdU阳性心肌细胞（新生细胞）。免疫组化显示：心外膜和心包膜组织中存在大量的Ki67阳性的分裂活跃细胞。心外膜和心包膜组织中的SCA-1和c-kit阳性细胞少，主要为KDR（flk-1）的阳性细胞，这些细胞呈克隆样增生，同一区域同时存在大量的cTnT阳性细胞，并发现部分KDR阳性细胞向心肌组织中迁移，提示这些心包起源的细胞可能参与了心脏的修复过程。结论心包膜组织在心脏自我修复过程中能起重要作用，其主要机制可能与心包膜KDR阳性心脏干细胞有关。Objective To define the protective role of pericardial tissue and identify the subcellular population with potential contribution to cardiac protection after injury in a rat model. Methods Myocardial infarction （MI） was created by the ligation of left anterior descending artery （LAD） in rats while the pericardial sac was either completely removed （ -PC, n = 10） or surgically closed after ligation （ ＋ PC, n = 8 ）. The follow-up functional and structure benefits were analyzed by echocardiography and 2, 3, 5- triphenyl tetrazoliumch（TTC） and bromodeoxyuridine （BrdU）staining. The contributions of cardiac stem cells （sca-1, c-kit and KDR ） were evaluated by immunohistochemistry. Results The integrity of pericardial sac showed significant benefits of cardiac contractile function （ejection fraction and short axis fractional shortening） in comparison to the controls （52 ± 12 vs 37± 12 and 36 ± 14 vs 25 ± 13, both P 〈 0.05）. The observed functional amelioration after MI was obvious based on structural repair examined by TFC staining and BrdU incorporation, showing significantly more de novo eardiomyoeytes in ± PC rats. Interestingly, we have immunohistologically identified a sub-population of KDR ＋ （flk-1 ＋ ） cells in pericardial tissue which clonegenically distributed and mildly expressed cardiac specific proteins （eTnT）. It suggested that the KDR ＋ cells might act as cardiac progenitors and therefore play an important role in cardiac repair. Meanwhile, rare SCA-1 and e-kit positive ceils were detected in pericardial tissue. Conclusion The intact pericardial tissue exerts protective effects after MI. It may be related with a specific cell population of KDR ＋ cells from pericardial tissue.

关 键 词：心包 心肌梗死 血管内皮生长因子受体2 干细胞 

分 类 号：R542.22[医药卫生—心血管疾病]