移植过表达缝隙连接蛋白43的骨髓间充质干细胞治疗大鼠心肌梗死后心力衰竭  

Therapeutic effect of transplantation of bone marrow mesenchymal stem cells over-expressing Cx43 on heart failure in post-infarction rats

作　　者：毛奕[1] 李松南[1] 毛晓波[1] 曾秋棠[1] 李裕舒[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院心内科,武汉430022

出　　处：《中华医学杂志》2011年第28期1982-1986,共5页National Medical Journal of China

基　　金：湖北省生物靶向治疗研究重点实验室开放基金（2008802）

摘　　要：目的 观察移植过表达缝隙连接蛋白43（Cx43）的骨髓间充质干细胞（BMSC）对心肌梗死后心力衰竭大鼠的治疗作用.方法 将60只SD大鼠分为4组,每组15只.假手术组;DMEM/F12组：注射DMEM/F12培养基;EGFP（增强的绿荧光蛋白）组：移植转染EGFP 基因的BMSC;Cx43组：移植转染Cx43基因的BMSC.采用结扎前降支的方法,建立心肌梗死模型,于梗死后30 min,行细胞移植.移植后4周,超声心动图检测心脏功能并取心脏组织.Masson染色检测梗死面积及胶原纤维含量.激光共聚焦显微镜观察EGFP基因及Cx43的表达.RT-PCR检测移植区心肌组织Cx43 mRNA含量.结果 EGFP组和Cx43组心功能明显改善[左室射血分数分别为（76.0±6.9）%、（82.9±5.0）%,P＜0.05],心肌梗死面积缩小,胶原纤维含量降低[分别为（13.6±4.7）%、（15.9±3.2）%,P＞0.05],Cx43组心脏重构指标改善更明显.激光共聚焦显示EGFP组和Cx43组均有BMSC存活,并与宿主心肌组织间形成缝隙连接.DMEM/F12 组Cx43 mRNA水平较假手术组显著降低（0.18±0.05比0.78±0.14,P〈0.01）,EGFP组Cx43 mRNA的含量与DMEM/F12 组相比差异无统计学意义（0.20±0.09 比 0.18±0.05,P〉0.05）.Cx43组Cx43 mRNA水平较DMEM/F12 组及EGFP组明显增加（0.39±0.14 比 0.18±0.05,P〈0.01;0.39±0.14比0.20±0.09,P〈0.05）.结论 过表达Cx43 的BMSC移植改善心力衰竭的效果更为明显,可能与BMSC改善了移植区缝隙连接表达有关.Objective To explore the therapeutic effect of transplantation of bone marrow mesenchymal stem cells （BMSCs） over-expressing Cx43 on heart failure in post-infarction rats. Methods Sixty SD rats were randomly divided equally into 4 groups： sham group , DMEM/F12 group injected with DMEM/F12, EGFP group with transplanted EGFP transfected BMSCs and Cx43 group with transplanted Cx43 transfected BMSCs. Myocardial infarction model was established by ligating anterior descending branch and the cells were transplanted after 30 minutes. At Week 4 post-infarction, the heart functions of rats were evaluated by echocardiography. After the rats were sacrificed, their tissue samples were collected. The areas of myocardial infarction and the levels of collagen fiber content were measured. And the expressions of EGFR and Cx43 were observed under laser confocal microscopy. The level of Cx43 mRNA was measured by reverse transcription-polymerase chain reaction （RT-PCR）. Results As compared with the DMEM/F12 group, cardiac function was improved significantly, myocardial infarct area shrunk and collagen fiber content decreased significantly in the EGFP and group in Cx43 groups the . Survival of BMSCs and the formation of gap junction between BMSCs and the host myocardium could be observed under laser confocal microscopy both in EGFP group and Cx43 groups. And the post-infarction, expression of Cx43 mRNA in myocardial tissue decreased significantly in the group DMEM/F12, when compared with sham group（0.18±0.05 vs 0.78±0.14, P〈0.01）. There was no significant difference on expression of Cx43 mRNA between DMEM/F12 group and EGFP group （0.18±0.05 vs 0.20±0.09, P〉0.05）. The lever of Cx43 mRNA was higher in group Cx43 than in group DMEM/F12 and group EGFP（0.39±0.14 vs 0.18±0.05, P〈0.01; 0.39±0.14 vs 0.20±0.09, P〈0.05）. Conclusion Transplantation of BMSCs attenuates ventricular remodeling and improves cardiac functions. It may result from the over-expression of Cx43 gene through its effects of improving g

关 键 词：干细胞 连接蛋白类 心肌梗死 心力衰竭 

分 类 号：R542.22[医药卫生—心血管疾病] R541.6[医药卫生—内科学]