移植时机对骨髓单个核细胞治疗心肌梗死效果的初步研究

Effect of Transplantation Timing on Efficacy of Myocardial Regeneration With Bone Marrow Mononuclear Cells

目的：研究经冠状动脉移植骨髓单个核细胞治疗心肌梗死的最佳时间窗。方法：结扎小型猪冠状动脉前降支90min再灌注制备心肌梗死模型，分为2小时移植组、2小时对照组、1周移植组和1周对照组，每组7只。移植组在结扎后2小时和1周经冠状动脉移植（8-10）×10^7个PKH26标记的骨髓单个核细胞，对照组注射等体积培养基。结扎后6周检测心功能变化并行病理检查。结果：两个移植组在心肌梗死区均可找到移植细胞，其Ⅷ因子和desmin免疫组化染色均为阳件。血流动力学指标显示：结扎后6周较结扎后90分钟相比，2小时移植组的左心审压力最大下降速度和心排量显著升高（P〈0．05）；1周移植组的左心室舒张末压和心排量显著改善（P〈0．05）。超声心动图指标显示结扎后6周时2小时移植组的每搏排血量和心排量显著高于2小时对照组（P〈0．05）；1周移植组结扎后6周-结扎前射血分数的差值明最高于1周对照组（P〈0．05）。两移植组结扎后6周的各项指标均无显著差异（P均〉0．05）。1周移植组梗死区的小血管数量明显高于2小时移植组（P〈0．01）。结论：住结扎后2小时和1周时经冠状动脉移植的骨髓细胞均能定植于心肌梗死区，并可向心肌细胞和血管内皮细胞方向分化，有改善心功能的潜能。在结扎后1周移植能吏有效地促进小血管新生。

Objective： To investigate the best timing for intracoronary transplantation of bone marrow mononuclear cells （BM-MNCs） atier myocardial infarction. Methods ： A 90-minute left anterior descending coronary artery ligation was undertaken to produce acute myocardial infarction and followed by reperfusion in 28 swine which were divided into 4 groups ： 2 hour transplantation group （ n = 7）, 2 hour control group （n =7）, 1 week transplantation group （n =7） and 1 week control group （n =7）. （8 - 10） × 10^7 BM-MNCs labeled with PKH26 previously in transplantation group or culture medium of the same volume in control group were intracoronarily infused into infarction-related arteries 2 hour and 1 week after ligation. Six weeks after ligation, histological characteristics and heart function were studied. Results： In the specimens of two transplantation groups, labeled cells were tound in the intarcted region. Immunochemical staining showed that factor Ⅶ and desmin were positive, The histological findings were similar between the two transplant ation groups. The hemodynamic parameters showed that left ventricular -dp/dmax and cardiac output （CO） of the 2 hour transplantation group at 6 weeks after ligation were increased （ P 〈 0. 05 ） in comparison with those at 90 minutes after ligation, so did left ventricular end-diastolic pressure and CO of 1 week transplantation group. The echocardiographic parameters showed in 2 hour transplantation group, stroke volume and CO at 6 weeks after ligation were increased（ P 〈 0. 05 ） in comparison with those in the control group, In I week transplantation group, before and 6 weeks after ligation ejection fraction was significontly increased （P 〈 0. 05 ）in comparison with that in 1 week control group. Between two treatment groups, no significant difference was lbund on hemodynamic parameters and echncardingraphie parameters. The number of vessels of I week transplantation group was larger than that of 2 hour transplantation group （P 〈 0.01 ）. Conclusion： Autologous BM-MNCs after being intracoronarily transplanted into ischemic region at 2 hours or 1 week after ligation could engraft, grow and differentiate into cardiomyogenic cells and endothelial cells, and have clinical potential in improving heart function. Transplantation at 1 week after ligation can promote angiogenesis more effectively.