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目的比较骨髓干细胞动员与骨髓单个核细胞移植对兔心肌梗塞的治疗作用,探讨更有效、更适用的干细胞治疗心肌梗塞的方法。方法将30支新西兰白兔采用结扎前降支的方法制作心肌梗塞模型,随机分为动员组、移植组和对照组,动员组(n=10)心梗后3h开始皮下注射粒细胞集落刺激因子(G-CSF)30μg(/kg·d),连续使用5d,第5天抽取静脉血约10mL,分离单个核细胞(mononuclearcells,MNCs)用5-溴脱氧尿嘧啶核苷(bromodeoxyuridine,Brdu)标记后,经静脉注入动物体内。移植组(n=10)心梗后7￣10d,抽取骨髓3￣5mL,分离MNCs用Brdu标记,然后开胸将细胞移植至梗死区,对照组(n=10)不采取任何治疗措施。心梗后1周及5周采用超声心动图(UCG)检查了解心脏功能变化,5周时作血液动力学测定,取心脏作免疫组织化学鉴定。结果心梗后5周,动员组左室射血分数(EF)与1周时相比明显增加,移植组无变化,对照组显著下降。5周时动员组及移植组左室舒张末压(LVEDP)、+dp/dtmax和-dp/dtmax与对照组相比均有显著变化。动员组及移植组在心肌梗死区均发现有Brdu标记的阳性细胞,两组梗死区血管密度明显高于对照组,但均未发现有新生的平滑肌细胞及心肌细胞。结论骨髓干细胞动员治疗心肌梗死,能通过促进梗死区血管新生,明显改善心脏功能,骨髓单个核细胞移植可避免心功能的恶化,但在改善心功能方面的作用有限,骨髓干细胞动员可能为心肌梗塞的治疗提供一种更适用的无创性的手段。
Objective To compare the therapeutic effects of mobilization of bone marrow stem cells and bone marrow mononuclear cells transplantation on myocardial infarction in rabbits and to explore a more effective and suitable method of stem cell therapy for myocardial infarction. Methods Thirty New Zealand white rabbits were made into myocardial infarction model by means of anterior descending artery ligation. They were randomly divided into mobilization group, transplantation group and control group. The mobilization group (n = 10) started subcutaneous injection of granulocyte colony stimulating factor (G-CSF) 30μg (/ kg · d) for 5 consecutive days. On the fifth day, venous blood was collected for about 10mL. Mononuclear cells (MNCs) were isolated and labeled with bromodeoxyuridine (Brdu) After the intravenous injection of animals. In the transplantation group (n = 10), 7 to 10 days after myocardial infarction, 3 to 5 mL of bone marrow was sampled. MNCs were isolated and labeled with Brdu. Cells were then transplanted into the infarct area by thoracotomy. No treatment was given in the control group (n = 10). Cardiac function was assessed by echocardiography (UCG) at 1 week and 5 weeks after myocardial infarction. Hemodynamic analysis was performed at 5 weeks, and the heart was identified by immunohistochemistry. Results After 5 weeks of myocardial infarction, left ventricular ejection fraction (EF) in mobilization group was significantly increased compared with that at 1 week, but no difference was observed in the transplantation group and in the control group. Left ventricular end-diastolic pressure (LVEDP), + dp / dtmax and -dp / dtmax in mobilization group and transplantation group at 5 weeks were significantly different from those in control group. Brdu-labeled positive cells were found in both the mobilized group and the transplantation group in the myocardial infarction area. The density of vascular dementia in the two groups was significantly higher than that in the control group, but no newborn smooth muscle cells and cardiomyocytes were found. Conclusion The mobilization of bone marrow stem cells in the treatment of myocardial infarction can significantly improve cardiac function by promoting angiogenesis in infarct area. However, bone marrow mononuclear cells transplantation can prevent the deterioration of cardiac function, but its function in improving cardiac function is limited. The mobilization of bone marrow stem cells may be myocardial infarction The treatment provides a more applicable noninvasive means.