骨髓单个核细胞移植治疗大鼠心肌梗死的时效性研究

Chronergy of bone marrow mononuclear cells transplantation in treatment of myocardial infarction

目的:探讨不同时间点移植骨髓单个核细胞(bone marrow mononuclear cells, BMMCs)对心肌梗死后的心功能的影响。方法:取成年雄性近交系Wistar大鼠股骨和胫骨,常规抽取骨髓,分离制备BMMCs悬液。将成年雄性近交系Wistar大鼠64只随机分为空白对照组(组Ⅰ,n=10)、梗死对照组(组Ⅱ,n=18)、即刻移植组(组Ⅲ,n=18)和两周移植组(组Ⅳ,n=18)。用结扎冠状动脉左前降支的方法建立大鼠心肌梗死模型,在建模后即刻和2周分别将10μl BMMCs液(6×106个细胞)植入组Ⅲ和组Ⅳ的梗死周边区,组Ⅱ于建模后14 d植入等量的磷酸盐缓冲液(PBS)。用心脏超声和血流动力学检查观察细胞移植后4周的心脏功能改变。结果:骨髓单个核细胞移植4周后,与组Ⅱ、组Ⅲ相比,组Ⅳ左室功能重建指标[左室射血分数(EF)、左室短轴缩短率(FS)、左室前壁厚度(LVAWT )]和血流动力学检查指标[左室收缩压(LVSP)、左室舒张末压(LVEDP)和左室舒张压力时间变化最大速率±dp/dtmax]均明显改善(P<0.05);而组Ⅱ、Ⅲ间上述指标相比无显著差异。结论:心肌梗死后2周骨髓单个核细胞移植治疗效果优于即刻移植,可能是由于在心肌梗死后1周时炎症反应最重,而2周时逐渐减弱。

Objective:To approach the effect of bone marrow mononuclear cells(BMMCs)transplantation on cardiac function at different time points after myocardial infarction. Methods:The BMMCs were extracted from the femur and the tibia of the adult male inbred strain Wistar rats by routine methods under sterile environment and were used to prepare suspension. Sixty-four adult male Wistar rats were divided into 4 groups at random: Blank (group Ⅰ,n=10),Control/Infarct (group Ⅱ,n=18),Instant transplantation (group Ⅲ,n=18) and 2-week-transplantation(group Ⅳ,n=18). Myocardial infarction was induced by ligating left anterior descending coronary artery. After that, groupⅡwere injected with 10 μl phosphate buffered saline(PBS); group Ⅲ and groupⅣ were transplanted with BMMCs (6×106 cells)/10 μl instantly and 2 weeks later separately. Four weeks after BMMCs transplantation, all groups received echocardiography and haemodynamics examination for evaluation of cardiac function changes. Results:Four weeks after BMMCs transplantation, the EF,FS and LVAWT and left ventricular remodeling were improved obviously in group Ⅳcompared with thosed in groupⅡ and group Ⅲ(P<0.05). The data of haemodynamics, including LVSP,LVEDP and ±dp/dt max, were also improved(P<0.05). There were no significant difference between groupⅡ and group Ⅲ concerning the above parameters. Conclusion: The therapeutic effect of transplanting BMMCs is better when the transplantation is done 2 weeks after myocardial infarction than it is done instantly after infarction, which may be due to that the inflammatory reaction is the greatest in the first week and subsides in the second week after myocardial infarction.