经静脉移植骨髓间充质干细胞向心肌梗死区趋化的组织学观察  

Histological observation on migration of bone marrow mesenchymal stem cells transplanted through vein to myocardium infarction region

作　　者：徐瑾[1] 王彬尧[1] 陈颖敏[1] 李洪波[1] 何奔[1] 

机构地区：[1]上海交通大学医学院附属仁济医院心内科,上海200001

出　　处：《心脏杂志》2009年第1期46-50,59,共6页Chinese Heart Journal

基　　金：上海市自然科学基金项目资助(02ZB14038)

摘　　要：目的采用2-脱氧5氮杂胞苷(5-aza-2’-deoxycytidine,5-aza-CdR)诱导的骨髓间充质干细胞(MSCs)经尾静脉移植入不同时期的心肌梗死(MI)后心衰大鼠中,观察其向病损心肌的趋化作用及其在局部分布的特点,探讨其对心肌α-肌球蛋白重链(α-MHC)mRNA表达的影响。方法培养Wistar大鼠的MSCs,用0·3μmol/L的5-aza-CdR两次诱导第2代的MSCs。用溴氮胞苷(BrdU)标记后,经尾静脉植入MI后不同时期的心衰大鼠中,实验分为MI1d、8d、3周、1月后移植组及MI3周、1月后DMEM假移植组。采用免疫组化染色法检测移植后3d及1月的MSCs在大鼠心肌中的分布情况,并用RT-PCR检测移植1月后MI局部α-MHCmRNA水平的变化。结果在MI后不同时期(1d内、8d、3周、1月),通过尾静脉给予相同数量的MSCs,3d后在各组大鼠的心肌中均发现抗BrdU+的移植细胞。移植的MSCs主要分布在心肌受损区域,分布特点与移植时心肌的病理特点有一定的关系。急性、亚急性期,有较多的移植细胞,与自身细胞均匀分布。进入慢性期,移植细胞沿着纤维方向线样排列,呈团簇样分布,数目较急性期减少。移植后1月,各组大鼠心脏中仍有抗BrdU+的移植细胞,移植细胞分布的特点与移植后3d所观察的结果相似。研究发现,MI区域rattusα-MHCmRNA的表达,与MI3周移植的MSCs相比,在MI1d或8d后移植,差异无显著性。MI3周后移植MSCs,rattusα-MHCmRNA的表达较DMEM假移植组有明显提高(P<0.01),但在MI1月后移植与假移植组差异无显著性。结论在不同的MI时间段经尾静脉植入MSCs,其能向心肌趋化,主要分布在心肌的受损区域,分布特点与移植时心肌的病理特点有关。MI后早期给予MSCs移植。AIM To investigate hemotaxis of 5-aza-2＇-deoxycytidine （5-aza-CdR） induced MSCs to damaged myocardium of infarction-induced heart failure in rats through tail vein transplantation and to study the distribution characteristics and the transplantation effect on rattus α-MHC mRNA expression in infarction region. METHODS Wistar rat MSCs were cultured in vitro and the second passage MSCs were incubated together with 5-aza-CdR （0.3 μmol/L） for two times. The induced MSCs labeled with bromodeoxyuridine （BrdU） were then transplanted through tail vein into the rats of infarction-induced heart failure at different time point （ 1 d, 8 d, 3 w and 1 m after myocardial infarction）. Three days and 1 month after transplantation, the homing ability of MSCs to the damaged myocardium and the distribution characteristics were studied by immunohistochemistry, α-MHC mRNA expression in the infarction region was also detected 1 month after transplantation by RT-PCR. RESULTS Three days after MSCs transplantation at different time periods, anti-BrdU positive cells were found in all groups. The donor MSCs were mainly in the damaged myocardium. In acute or subacute period, many donor MSCs were well mixed with the cells. In chronic period, donor MSCs decreased in number and aligned with fibers. One month after transplantation, anti-BrdU positive donor cells could still be seen in some rats. The distributing characteristics were similar to those 3 days after transplantation. No significant difference of rattus α-MHC mRNA expression was found in infarction region between MSCs transplantation 1 d or 8 d after infarction and MSCs transplantation 3 w after infarction. The rattus α-MHC mRNA expression in infarction region in MSCs transplantation 3 w after infarction improved and was significantly different compared with that in DMEM transplantation group （ P 〈 0.01 ）. But there was no significant difference between the MSCs transplantation group and DMEM transplantation group when transplanted 1 month after infarction.

关 键 词：骨髓间充质干细胞 细胞移植 心肌梗死 趋化 

分 类 号：R541.61[医药卫生—心血管疾病] R459.9[医药卫生—内科学]