不同CD34+干细胞移植途径对缺血性心肌病大鼠心功能影响的研究

目的 探讨同种异体CD34+干细胞不同移植途径对心肌梗死后心力衰竭大鼠心功能的影响,同时评价干细胞移植的有效途径和安全性.方法 Wistar雄性大鼠64只被随机分成3组:干细胞移植组(30只);急性心肌梗死模型组(20只);假手术组(14只).移植组和模型组结扎左冠状动脉(冠脉)前降支造成缺血性心肌病模型;假手术组只开胸,不结扎冠脉.另选同种异体大鼠30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制成干细胞悬液,在冠脉结扎后7 d分别经股静脉和心外膜注入到移植组大鼠体内,模型组和假手术组注入等量磷酸盐缓冲液(PBS).于制模前、干细胞移植术后1、2和4周分别行心脏超声检查,术后4周进行血流动力学测定.结果 与模型组比较,心肌梗死后4周移植组左室射血分数(LVEF)、左室短轴缩短率(ΔFS)、左室收缩期末压(LVESP)和左室内压最大上升速率(+dp/dt max)明显提高(P均＜0.01),左室收缩期末直径(LVESD)、左室舒张期末压(LVEDP)、左室内压最大下降速率(-dp/dt max)和左室等容舒张时间常数(Tc)均明显减小(P均＜0.01);股静脉移植和心外膜移植两种途径对心功能的影响差异无统计学意义(P均＞0.05).结论 经股静脉和心外膜两种途径移植外周血干细胞是安全可行的,二者均能有效地改善心功能,有助于梗死心肌的修复.

Effects of different delivery routes of CD34+ stem cells on cardiac function in the ischemic cardiomyopathy of rats

OBJECTIVE: To compare the effects of CD34-positive stem cells delivered by different routes on cardiac function in rats with ischemic cardiomyopathy, and to evaluate the efficacy and safety of stem cell transplantation. METHODS: Sixty-four male Wistar rats were randomized into cell infusion group (n=30), acute myocardial infarction (AMI) model group (n=20) and sham operation group (n=14). AMI model was reproduced by ligation of left anterior descending coronary artery. CD34+ stem cells mobilized with granulocyte-colony stimulating factor (G-CSF) were purified by immunomagnetic beads in 30 donor rats. Seven days after the injury about (7-9)x10(7) CD34+ stem cells were infused through the femoral vein or through epicardium of recipient rats respectively. Cardiac function was evaluated before AMI, 1, 2 and 4 weeks after cell delivery. Hemodynamic parameters were determined 4 weeks after cell infusion. RESULTS: Compared with model group, left ventricular ejection fraction(LVEF), fractional shortening (DeltaFS), left ventricular end-systolic pressure (LVESP) and maximal positive change in filling pressure versus time (+dp/dt max) were improved significantly (all P<0.01), whereas left ventricular end-systolic dimension (LVESD), left ventricular end-diastolic pressure (LVEDP), maximal negative change in filling pressure versus time (-dp/dt max), time constant of left ventricular relaxation (Tc) were lowered in cell infusion groups (all P<0.01). There were no significant differences in cardiac function indexes between intravenous infusion and transepicardial injection group (all P>0.05). CONCLUSION: Intravenous and transepicardial delivery of hematopoietic stem cells (HSC) can significantly improve cardiac function, and both methods may be safe and effective for the treatment of AMI.