老龄兔骨髓间充质干细胞移植治疗心肌梗死的最佳时间

Best time of mesenchymal stem cells transplantation for treatment of myocardial infarction in aged rabbits

目的:探讨老龄兔骨髓间充质干细胞(MSCs)移植治疗心肌梗死的最佳时间,为细胞移植治疗心肌细胞坏死性相关疾病提供前期的实验依据。方法:选择月龄大于或等于36个月的新西兰大耳白兔30只(36月龄兔相当人60岁左右,为老龄兔),建立心肌梗死模型,将造模成功兔随机分为6组(空白对照组、1 d组、1周组、2周组、3周组、4周组),每组5只;取标记后的MSCs细胞(密度为2×107.mL-1)200μL,分别多点注射于心肌梗死后1 d、1周、2周、3周、4周的心脏梗死区,空白对照组注射等量生理盐水。8周后进行心功能参数、心脏房室瓣血流率及血液动力学指标检测。结果:与对照组比较,1 d移植组心功能参数、心脏房室瓣血流率及血液动力学指标高于对照组(P<0.05);1周、2周及3周移植组心功能参数、心脏房室瓣血流率及血液动力学指标明显高于对照组(P<0.01);4周移植组与对照组比较心功能虽有提高,但差异无显著性(P>0.05);1周、2周及3周移植组心功能参数、心脏房室瓣血流率及血液动力学指标高于1 d移植组(P<0.05);1周、2周、3周三组之间比较差异无显著性(P>0.05)。结论:心肌梗死后不同时间进行相同剂量细胞移植时,1 d^3周行MSCs细胞移植治疗均能改善心功能,以第1~3周移植效果最佳。

Objective To investigate the best time of the mesenchymal stem cells （MSCs） transplantation after myocardial infarction （MI）, in order to provide prophase experimental basis for treatment of the diseases correlating to cadiocyte necrosis by cells transplantation. Methods Thirty New Zealand big-ears albino rabbits, which aging were older than or equal to 36 months were selected （a 36-month rabbit is the advanced age rabbit, equaling a person 60 years old）. Model of MI was made by ligating anterior descending branch. The model rabbits were randomly divided into six groups （control group, 1 d group, 1-week group, 2-week group, 3-week group; and 4-week group, n= 5）. 200 μL cells after marked were drawed and injected in multiple positions of myocardium after MI in 1 d group, 1-week group, 2-week group, 3-week group and 4-week group separately. The rabbits in control group were injected with saline of equal quantity. The cardiac functional parameters, blood flow rate of atrioventricular valve and the hemodynamics at eighth week in various groups were measured. Results Compared with control group, the treatment of MSCs transplantation for MI improved the heart function. The cardiac functional parameters, blood flow rate of atrioventricular valve and the hemodynamics in 1 d group was higher than those in control group （P〈0.05） ; the cardiac functional parameters, blood flow rate of atrioventricular valve and the hemodynamics in 1-week group, 2-week group, and 3-week group were significantly higher than those in control group （P〈0.01） ; there was no significant difference between 4-week group and control group （P〉0.05） . The cardiac functional parameters, blood flow rate of atrioventricular valve and the hemodynamics in 1-week, 2-weeks and 3-weeks groups were better than those in 1 d group （P〈0.05）, however there was no significant difference between them （P〉0.05）. Conclusion In the condition of the same cell-density but the different time of MI, the transplantation time window is 1 d-3 weeks after MI, which is advantageous to the amelioration of heart function, the best time of transplantation was 1-3 weeks after MI.