骨髓干细胞动员治疗急性心肌梗死

Effect of Bone Marrow Stem Cell Mobilization on Acute Myocardial Infarction

目的研究骨髓干细胞动员治疗急性心肌梗死的可行性。方法24只新西兰大白兔随机分为实验组和对照组,结扎实验动物前降支制作急性心肌梗死模型。实验组动物心肌梗死后24 h开始皮下注射重组人粒细胞集落刺激因子,100μg/Kg,连续注射10 d;对照组动物心肌梗死后24 h开始注射等量生理盐水,连续注射10 d。检测实验动物外周血骨髓干细胞动员情况、心功能变化及心肌梗死区毛细血管密度。结果两组实验动物骨髓干细胞动员前外周血有核细胞计数与单个核细胞比例近乎相等,差别无统计学意义;实验组动物重组人粒细胞集落刺激因子皮下注射,外周血骨髓干细胞一般在5 d左右达到峰值,外周血有核细胞计数(63.10±16.72)×109/L及单个核细胞比例(97.1±2.88)%明显高于动员前,同时亦明显高于对照组;两组实验动物心肌梗死模型术后4周左心室射血分数与术前相比明显降低,分别为(50.11±6.37)%vs(42.27±9.35)%,实验组高于对照组,差别有统计学意义。实验组心肌梗死区内有大量岛状存活心肌,毛细血管计数(3.68±0.78)/HP,而对照组心肌梗死区内岛状存活心肌少,坏死心肌由均质瘢痕组织替代,毛细血管计数(1.38±0.87)/HP,对照组明显少于实验组,P<0.05。结论重组人粒细胞集落刺激因子(100μg/Kg)皮下注射可有效动员骨髓干细胞入外周血参与梗死心肌修复,增加心肌梗死区毛细血管密度,改善心功能。

Objective To investigate the effects of bone marrow stem cell mobilization on infarcted myocardium and cardiac function. Methods New Zealand rabbits, 24 cases, wen divided equally into two groups at random. Ligating left anterior descending branch of coronary artery with 3-0 noninvasive medical sutures induced acute myocardial infarction model. In the test group recombinant human granulocyte colony-stlmulating factor was given by subcutaneous injection 24 hours after operation, once per day in successive 10 days. In the control group saline was given in the same way. Bone marrow stem cells mobilization was detected by karyote counts and the fraction of mononuclear cell in total nucleated cells in peripheral blood. The change of heart function and capillary density in infarcted myocardial areas were also measured. Results There were not statistically significant between two groups in karyote counts and mononuclear cell ratio in peripheral blood before bone marrow stem cells mobilization. In test group, 5 days after recombinant human granulocyte colony-stimulating factor subcutaneous injection, bone marrow stem cells mobilized significantly. The karyote counts（63.10 ± 16.72） × 10^9/L and mononuclear cell ratio （97.1 ± 2.88）% were higher than pre-mobilization, also higher than the contrast group at the same time. 4 weeks after acute myocardial infarction, the ejection fraction of left ventricular cut down obviously in both groups, but there were statistically significant between the test group and the contrast group （50.11 ± 6.37）% versus（ 42.27 ± 9.35 ）%, respectively. The ejection fraction of left ventricular in the test group was improved compared to the control group, with lots of survival myocardium islands and increased capillary density in the infarcted myocardial areas. There were statistically significant in the capillary density between the test group and the contrast greup（3.68 ± 0.78 vs 1.38 ± 0.87, respectively. P 〈 0.05）. Conclusion This experimental study indicated that recombinant human granulocyte colony-stimulating factorl （100 μg/kg）subcutaneous injection could effectively mobilized bone marrow stem ceils to peripheral blood circulation, repairing infarcted myocardium, increasing capillary density and improving heart function.