造血干细胞移植对急性心肌梗死大鼠心功能影响的研究

Improvement of cardiac function of the infarcted rats by the transplantation of hematopoietic stem cells

目的探讨同种异体CD34+干细胞移植对急性心肌梗死(AMI)大鼠心功能的影响,同时评价干细胞移植的有效性和安全性。方法Wistar雄性大鼠29只,随机分成3组:干细胞移植组(10只),急性心肌梗死对照组(10只),假手术组(9只)。移植组和对照组结扎左冠状动脉前降支造成急性心肌梗死模型。另选同种异体大鼠10只,将粒细胞集落刺激因子(G-CSF)动员的外周血CD34+干细胞经免疫磁珠法分离纯化后,在冠脉结扎后7 d,经心外膜注入到移植组大鼠体内,对照组和假手术组注入等量磷酸盐缓冲液(PBS)。心梗术前,干细胞移植术后12、和4周分别行心脏超声检查,术后4周行血液动力学测定。结果心肌梗死后4周,与对照组比较,移植组左室射血分数(LVEF)、左室短轴缩短率(FS)、左室收缩末压(PES)和左室压力最大上升速率(dp/dtmax)明显提高(P<0.01),左室收缩末直径(LVESD)、左室舒张末压(PED)、左室压力最大下降速率(dp/dtmin)和左室等容舒张时间常数(Tc)均明显减小(P<0.01)。结论经心外膜途径移植外周血干细胞是安全可行的,它能有效地改善心功能,为AMI的治疗提供一条行之有效的新途径。

Objective To investigate the effects of CD34 - positive stem cells on cardiac function of the infarcted rats, and to evaluate the efficacy and safety of stem cell transplantation. Methods Twenty - nine male Wister rats were divided at random into cell infusion group （ n = 10）, control group（ n = 10） and sham - operated group（ n = 9）. AMI was induced by ligation of left anterior descending coronary artery. CD34- positive stem cells mobilized by grsanulocyte - colony stimulating factor（ G- CSF） were purified by immunonmagnetic beads in donor rats. Seven days after the injury about （7 - 9） × 10^7 CD34 - positive stem cells were infused through the epicardium of recipient rats. Cardiac function was evaluated before MI, lw, 2w and 4w after cell delivery. Hemndynamic measurement was performed at 4w after cell infusion. Results Compm＇ed with control group, left ventricular ejection fraction（LVEF）, fractional shortening（F S）, left ventricular end systolic pressure（PES） and dp/dtmax were improved significantly（ P 〈 0.01）, whereas left ventricular end systolic diameter（ LVESD）, left ventficular end diastolic pressure（PED） , dp/dtmin, time constant of left ventricular relaxation（Te） were lower （ P 〈 0.01）in cell infusion group. Conclusion Transepicardial delivery of hematopoietic stem cells （ HSC） can significantly improve cardiac function and it is a safe and effective method for the treatment of AMI.