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目的对比研究经冠脉骨髓单个核细胞(BM-MNC)和间充质干细胞(MSC)移植对实验性急性心肌梗死(AMI)心功能的影响及其机制。方法选用12只雄性冀中白猪随机分为:正常对照组、AMI模型组、BM-MNC组、MSC组各3只,经导管球囊封闭前降支制作AMI的动物模型,于梗死后1 h直接冠脉球囊成型术后经OTW球囊注入骨髓干细胞。分别于术前及术后4 w经心脏超声检测心功能,4 w后取材行光、电镜病理学检查,实时定量RT-PCR检测心肌血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)mRNA表达。结果4 w时干细胞组比AMI模型组室壁运动异常指数显著减轻(P<0.05)、射血分数显著提高(P<0.01)。与AMI模型组相比:BM-M;NC和MSC组梗死区及梗死边缘区血管数显著增多、BM-MNC组增加比MSC组显著(P<0.01),心肌细胞凋亡指数显著降低,BM-MNC组及MSC组间无明显差异(P<0.01)。干细胞移植组梗死边缘区冠脉血管周围可见异常细胞生长,有毛细血管“芽生”现象,可见不成熟的心肌细胞和细胞凋亡。4 w时左室射血分数(LVEF)与心肌血管数成正相关(r=0.694 9,P=0.037 7),LVEF与心肌细胞凋亡指数成负相关(r=0.913 3,P=0.000 6)。BM-MNC组,心肌梗死区及梗死边缘区VEGF基因表达比其他三组均明显增加(梗死区F=4.23,P=0.045 6,边缘区F=5.66,P=0.022 3)。BM-MNC及MSC组心肌梗死区bFGF基因表达比梗死模型组显著增加(梗死区F=7.49,P=0.010 4)。结论经冠脉骨髓单个核细胞和间充质干细胞移植均可改善实验性AMI心功能;改善心功能的机理与梗死区及梗死边缘区VEGF及bFGF表达增加,血管密度增加,心肌细胞凋亡减少有关;骨髓单个核细胞移植的促血管增生作用优于间充质干细胞移植。
Objective To compare the effects of coronary artery marrow mononuclear cells (BM-MNCs) and mesenchymal stem cells (MSCs) transplantation on cardiac function in experimental acute myocardial infarction (AMI) and its mechanism. Methods Twelve male Jizhong white pigs were randomly divided into three groups: normal control group, AMI model group, BM-MNC group and MSC group. The animal models of AMI were established by catheter balloon anterior descending coronary artery. After 1 h After direct coronary balloon angioplasty, bone marrow stem cells were infused via OTW balloon. Cardiac function was measured by echocardiography before and 4 weeks after operation, and light and electron microscopy were performed 4 weeks later. The expressions of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) mRNA expression. Results Compared with the AMI model group, the abnormality of wall motion index (P <0.05) and the ejection fraction increased significantly (P <0.01). Compared with the AMI model group, BM-M significantly increased the number of blood vessels in the infarct and infarct border zones in the NC and MSC groups, and increased significantly in the BM-MNC group compared with the MSC group (P <0.01) There was no significant difference between -MNC group and MSC group (P <0.01). Stem cell transplantation infarct border zone around the coronary vessels showed abnormal cell growth, capillary “budding” phenomenon, we can see immature cardiomyocytes and apoptosis. The left ventricular ejection fraction (LVEF) at 4 w was positively correlated with the number of myocardial vessels (r = 0.694 9, P = 0.037 7). The LVEF was negatively correlated with the cardiomyocyte apoptosis index (r = 0.913 3, P = 0.000 6) . The expression of VEGF in BM-MNC group, myocardial infarction area and infarct border area were significantly higher than those in other three groups (F = 4.23 in infarction area, P = 0.045 6, F = 5.66 in marginal area, P = 0.022 3). The expression of bFGF in myocardial infarction area of BM-MNC group and MSC group was significantly higher than that of infarction group (F = 7.49, P = 0.010 4). Conclusion Transplantation of coronary bone marrow mononuclear cells and mesenchymal stem cells can improve experimental AMI cardiac function. The mechanism of improving cardiac function is associated with an increase in the expression of VEGF and bFGF in the infarct and infarct marginal areas, an increase in vascular density, and a decrease in cardiomyocyte apoptosis Related; bone marrow mononuclear cell transplantation is more effective than mesenchymal stem cell transplantation.