移植成血管基因修饰MSCs改善心肌梗死大鼠左室血流动力学参数的研究  

Improvement of hemodynamic parameters in left ventricle of rats with heart infarction by transplantation of MSCs modified by vascular endothelial growth factor

作　　者：高峰[1] 张近宝[1] 姜建青[1] 周凯[1] 唐柯[1] 赵璧君[2] 刘维永[2] 

机构地区：[1]成都军区总医院胸心外科,成都610083 [2]第四军医大学西京医院心脏外科研究所

出　　处：《西南国防医药》2012年第6期598-601,共4页Medical Journal of National Defending Forces in Southwest China

摘　　要：目的探讨大鼠心肌梗死模型缺血心肌局部移植血管内皮生长因子(vascular endothelial growth factor,VEGF)修饰的骨髓间充质干细胞(mesenchymal stem cells,MSCs)对左室血流动力学参数的影响。方法 Percoll液密度梯度离心法分离、贴壁培养Wistar近交系大鼠MSCs,真核表达载体pcDNA3.1(-)/hVEGF165转染MSCs。30只Wistar近交系大鼠随机均分为转染组(MSCs/VEGF组)、对照组(MSCs组)、无血清培养基组(DMEM组)。结扎前降支建立急性心肌梗死模型后在梗死区边缘区行5×106(40μl)细胞移植,DMEM组行等量培养基注射。移植前细胞行CM-DiI标记。移植1个月后行心脏B超测量EF值,经右侧颈内动脉左室内置管测量如下血流动力学参数:心率(heart rate,HR)、左室收缩末压(left ventricularend-systolic pressure,LVESP)、左室舒张末压(left ventricular end-diastolic pressure,LVEDP)、最大左室内压上升速率(+dp/dtmax)、最大左室内压下降速率(-dp/dtmax)。大体标本组织行HE、Masson染色。结果培养的MSCs呈典型贴壁生长成纤维细胞样外观,CM-DiI能近100%标记MSCs。移植后1个月MSCs/VEGF组较其余两组LVEF、LVESP、LVEDP、+dp/dtmax、-dp/dtmax值有显著性差异(P<0.05),大体标本HE、Masson染色染色病理变化亦明显优于其余两组。结论大鼠心肌梗死模型梗死心肌局部移植VEGF基因转染MSCs能显著改善左室血流动力学参数,进而改善心脏功能。Objective To discuss the effects of partially transplanted mesenchymal stem cells （MSCs） modified by vascular endothelial growth factor（VEGF） in ischemic myocardium on hemodynamic parameters of left ventricle in rat models of heart infarction. Methods MSCs from the inbred line Wistar rats were isolated by density gradient centrifugation with Pereoll hquid and received adherent culture, and then transfected by eukaryotic expression vector of pcDNA3.1 （ - ）/hVEGE165. Thirty inbred line Wistar rats were averagely and randomly divided into 3 groups：transfection group（ MSCs/VEGF group）, control group （MSCs group）and serum - free medium group（ DMEM group）. Their anterior descending branch was ligated to establish the model of acute heart infarction. After that, cell transplantation of 5 x 106（40 I^1）was made in the marginal zone of the infarction area. The DMEM group received the same volume of medium injection. Before the transplantation, all the cells were marked by CM - DiI. One month after the cell transplantation, left ventricular election fraction（LVEF） value was detected by cardiac type - B ultrasound. And the hemodynamics parameters belowwere detected by the left ventricular internal tube inserted through right internal carotid artery： heart rate （ HR）, left ventricular end - systolic pressure （ LVESP ）, left ventricular end - diastolic pressure （ LVEDP）, maximum upstroke velocity of left ventricular pressure （ ＋ dp/dtmax） and maximum breakdown velocity of left ventricular pressure （ - dp/dtmax）. Histochemical HE and Masson staining were performed in large specimens. Results The cultured MSCs showed typical adherent growth and fibroblast - like appearance, and could be marked by almost 100% of CM - DiI. One month after the transplantation, there were significant differences in LVEF, LVESP, LVEDP, ＋ dp/dtmax and -dp/dtmax between the MSCs/VEGF group and the other two groups （P 〈 0.05 ）. And in the MSCs/VEGF group, the pathological changes in HE an

关 键 词：血管内皮细胞生长因子 骨髓间充质干细胞 缺血心肌 血流动力学 细胞移植 

分 类 号：R541.4[医药卫生—心血管疾病]