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目的研究自体骨髓单个核细胞(BM-MNC)和间充质干细胞(MSCs)移植对急性心肌梗死(AMI)后心室重构的影响,探讨不同干细胞移植对心室重构影响的机理。方法以小型猪为研究对象,通过球囊导管压迫冠状动脉前降支的方法,建立小型猪AMI动物模型。在AMI 90 min时,经冠状动脉腔内进行自体BM-MNC和MSCs移植。于术前及干细胞移植后28 d,观察心功能、心肌微血管计数、心肌核因子_KB、心肌细胞凋亡、心肌血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)的mRNA表达。与心功能进行相关性分析。结果(1)术后28 d,BM-MNC组、MSCs组EDD均明显低于AMI模型组(P=0.005),EF明显高于模型组(P=0.0001;P=0.0017)。(2)BM-MNC移植组血管数比梗死组及MSCs组增加(梗死区P=0.000 1,边缘区P=0.000 1)。(3)BM-MNC组及MSCs组心肌细胞凋亡率比梗死模型组减少(梗死区P=0.000 1,梗死边缘区P= 0.000 1,正常区P=0.005 2)。(4)BM-MNC组及MSCs组NF-_KB阳性率比单纯AMI模型组显著降低(P=0.001)。(5)梗死模型组、BM-MNC组以及MSCs组的梗死区及梗死边缘区的VEGF基因表达量与正常对照组的相比增加(梗死区P=0.0001;梗死边缘区P=0.000 1)。BM-MNC及MSCs移植组,心肌梗死区的bFGF基因表达量比梗死模型组及正常对照组均显著增加(P=0.000 1)。LVEF与心肌细胞凋亡呈负相关(r=-0.441 1,P= 0.027 3),与心肌NF-_KB负相关(r=-0.579 6,P=0.000 6);与梗死区、边缘区血管数正相关(r=0.775 0,P=0.000 3);与VEGF表达正相关(r= 0.565 1,P=0.018 1);与bFGF表达正相关(r=0.573 5,P=0.016 1)。结论经冠脉自体BM-MNC及MSCs移植均可减轻心肌梗死后左心室重构,改善急性心肌梗死后心功能,增加心肌血管数量,增加梗死区及梗死边缘区VEGF及bFGF表达,减少心肌细胞凋亡。心功能的改善与干细胞移植后增加心肌血管数量、增加心肌VEGF及bFGF表达、减少心肌细胞凋亡以及减少心肌组织NF-_KB水平有关。
Objective To investigate the effects of autologous bone marrow mononuclear cells (BM-MNCs) and mesenchymal stem cells (MSCs) transplantation on ventricular remodeling after acute myocardial infarction (AMI) and to explore the mechanism of different stem cell transplantation on ventricular remodeling. Methods Small pigs were used as research object to establish animal model of AMI in miniature swine by balloon catheter compression of anterior descending coronary artery. At AMI 90 min autologous BM-MNC and MSCs were transplanted via the coronary artery. The levels of cardiac function, myocardial microvascular count, myocardial nuclear factor-κB, cardiomyocyte apoptosis, myocardial vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) mRNA were observed before and 28 days after stem cell transplantation expression. Correlation with heart function. Results (1) After 28 days, the EDD of BM-MNC group and MSCs group were significantly lower than that of AMI model group (P = 0.005). EF was significantly higher than that of model group (P = 0.0001; P = 0.0017). (2) The number of blood vessels in BM-MNC transplantation group increased more than that in infarction group and MSCs group (P = 0.000 in infarction area and P = 0.000 in marginal area). (3) The apoptosis rate of cardiomyocytes in BM-MNC group and MSCs group was lower than that in infarction group (P = 0.000 in infarction area, P = 0.000 in infarct border area, P = 0.005 2 in normal area). (4) The positive rate of NF-κB in BM-MNC group and MSCs group was significantly lower than that in AMI group (P = 0.001). (5) The expression of VEGF gene in infarction area and infarct border area of infarction model group, BM-MNC group and MSCs group increased compared with that of normal control group (P = 0.0001 in infarction area and P = 0.000 1 in infarct border area). The expression of bFGF gene in myocardial infarction area in BM-MNC and MSCs transplantation group was significantly higher than that in infarction model group and normal control group (P = 0.000 1). LVEF was negatively correlated with cardiomyocyte apoptosis (r = -0.441 1, P = 0.027 3), but negatively correlated with NF-κB (r = -0.579 6, P = 0.000 6) (R = 0.775 0, P = 0.000 3). The positive correlation with VEGF expression (r = 0.565 1, P = 0.018 1) was positively correlated with the expression of bFGF (r = 0.573 5, P = 0.016 1). CONCLUSIONS: Coronary auto-transplantation of BM-MNC and MSCs can relieve left ventricular remodeling after myocardial infarction, improve cardiac function after acute myocardial infarction, increase myocardial blood vessels, increase VEGF and bFGF expression in infarct and infarct marginal areas and decrease myocardial cells Apoptosis. The improvement of cardiac function is related to increasing the number of myocardial vessels, increasing the expression of VEGF and bFGF, decreasing the cardiomyocyte apoptosis and decreasing the level of NF-κB in myocardial tissue after stem cell transplantation.