静脉移植人羊膜间充质干细胞改善大鼠心肌梗死后心功能  

Intravenous transplantation of human amniotic mesenchymal stem cells improves cardiac function in rats with acute myocardial infraction

作　　者：方宁[1] 王钰莹[1] 陈代雄[1] 余丽梅[1] 章涛[1] 赵春华[2] 

机构地区：[1]遵义医学院附属医院贵州省细胞工程重点实验室,贵州遵义563003 [2]中国医学科学院基础医学研究所组织工程中心,北京100005

出　　处：《基础医学与临床》2013年第12期1516-1522,共7页Basic and Clinical Medicine

基　　金："重大新药创制"国家科技重大专项课题(2009ZX09503-025);贵州省科技厅计划发展项目(黔科合2003JGy005);贵州省科技厅公关项目[黔科合SZ字(2009)3017]

摘　　要：目的探讨人羊膜间充质干细胞(hAMSCs)静脉移植能否改善心肌梗死(MI)后心功能、减轻心肌纤维化和分化成心肌细胞。方法用流式细胞术和免疫组化染色对分离的hAMSCs进行表型分析和鉴定。结扎大鼠左冠状动脉前降支以建立MI模型,随机分为假手术组、模型组对照组和hAMSCs移植组,每组12只。成模后1周,移植组经舌下静脉注射2×106BrdU标记的hAMSCs。用超声心动图检查心功能,用HE和Masson染色观察心肌组织病理,用免疫荧光双染色检测hAMSCs在MI区的存活及向心肌细胞分化的标志物。结果 1)移植后1、4和6周,hAMSCs组射血分数和左室短轴缩短率均显著高于模型组(P<0.01);舒张期左室前壁厚度和收缩期左室前壁厚度也都明显大于模型组(P<0.01,P<0.05);2)hAMSCs移植后6周,纤维化面积明显少于模型组(P<0.01);3)hAMSCs移植后6周,MI区BrdU阳性细胞表达心肌特异蛋白连接蛋白-43、α-辅肌动蛋白和结蛋白。结论 hAMSCs静脉移植能改善心肌梗死后心功能和心室重构,在心肌梗死原位可分化为心肌细胞。Objectives To investigate whether intravenously transplanted human amniotic mesenchymal stem cells （hAMSCs） could improve cardiac function ，and reduce myocardial fibrosis in rats with acute myocardial infarction（MI）. Methods The phenotype of hAMSCs was analyzed by flow cytometry （FCM） .MI models were built by left anterior descending artery ligation in male SD rats. The rats were randomly divided into sham operation group, model group and hAMSCs transplanted group, with twelve in each group. At seven days after the MI, 2×106 of BrdU labeled hAMSCs or vehicle （control group） were intravenously administered to rats. At different times after transplantation, echocardiogram, histopathology, immunohistochemistry and immunofluorescence were performed to observe the effects of hAMSCs transplantation on cardiac function ,ventricular remodeling, and histopathologic change , as well as the survival and differentiation of the transplanted cells in the MI regions. Results ①The hAMSCs group showed a significant improvement in ejection fraction and left ventriccular fractinal shortening compared with those in the model group at 1w, 4w and 6w after transplantatio. In this group there were also a significant increase in left ventricular anterolateral wall thickness at diastole and left ventricular anterolateral wall thickness at systole.②Six weeks after hAMSCs transplantation, the percentage of fibrosis area was decreased singnifcantly compared with the model group.③the cardiac-specific protein connexin -43, α-actinin and desmin positive cells were detected in BrdU-labeled cells.Conclusion Intravenous transplantation of hAMSCs can improve cardiac function and myocardial fibrosis after MI , and transplanted hAMSCs may differentiate into cardiomyocytes in the myocardial infarction zone.

关 键 词：人羊膜间充质干细胞 心肌梗死 移植 分化 心功能 

分 类 号：R542.22[医药卫生—心血管疾病]