经冠状动脉自体骨髓造血干细胞移植对急性心肌梗死的疗效

Efficacy of intra-coronary autologous bone marrow mononuclear cells transplantation on acute myocardial infarction

目的探讨经冠状动脉自体骨髓造血干细胞(autologous bone marrow mononuclear cells,ABM-MNCs)移植对急性心肌梗死(acute myocardial infarction,AMI)患者的心功能超声学参数的影响及其作用机制。方法2004年6月～2006年3月,严格筛选出AMI35例,年龄在65岁以下,心肌梗死距此次手术的时间在1个月以内,左心室射血分数在0.45以下,随机分为2组(两组各有3名女性患者)。移植组18例,年龄(54±13)岁,AMI距本次手术时间(10±4)d,置入支架时经冠状动脉在梗死相关血管移植ABM-MNCs;对照组17例,年龄(57±11)岁,AMI距本次手术的时间(9±6)d,置入支架时经冠状动脉在梗死相关血管注入等体积生理氯化钠溶液;在术前及术后45d、90d为患者复查心脏彩超;术前、术后5、45、90d抽取患者全血,分离血浆,试验结束后用ELISA检测血浆血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)浓度。结果在术后45d和90d,的心输出量、短轴缩短分数、左心室射血分数、左心室收缩末期内径表明:移植组的心肌收缩功能改善优于对照组(P<0.05);在术后90d,左心室舒张末期内径表明:移植组的心肌舒张功能改善优于对照组(P<0.05);在45d和90d,二尖瓣环水平6位点S峰、E峰和A峰,移植组有部分位点改变优于对照组(P<0.05);术后90d,对照组左心室舒张末期内径和A峰较术前明显增大(P<0.05),提示发生心脏重构,而移植组增大不明显(P>0.05);术后5d、45d和90d,移植组VEGF浓度在高于对照组(P<0.05)。结论经冠状动脉ABM-MNCs移植能有效改善AMI后心脏的收缩和舒张功能。VEGF高表达可能与造血干细胞的作用机制有关。

Objectives To evaluate clinically the curative effect on ventficular function in acute myocardial infarction （AMI） patients by intra-eoronary autologous bone marrow mononuclear cells （ABM-MNCs） transplantation and approach it＇s mechanisms. Methods Thirty-five AMI patients （age≤65 years） with cardiac insufficiency were recruited consecutively and strictly from June 2004 to Mareh 2006, then were randomly divided into transplantation group and control group （each group 3 females respectively）. The time from AMI to operation was less than 1 month. For transplantation group （ 18 eases） , average age was （54±13）years, ABM-MNCs were transplanted in infarction related coronary artery while stent was implanted; and for control group （17 cases）, average age （57±11） years （P〉0.05）, but only equal volume of 0.9% normal saline was injected while stent was implanted. Results All patients accepted Doppler tissue imaging （DTI） by two ultrasonic experts randomly and one-blindly before operation and at the forty-fifth, ninetieth day after the operation. Before operation and at the fifth, forty-fifth, ninetieth day, all patients＇ blood were drawn out and centrifugalized, then 1 ml plasma from the patients＇ centrifugalized blood was got every time and stored in refrigerator below -20℃. After the test ended up, VEGF＇s concentration of all stored plasma was determined by VEGF ELISA. Results Average time from AMI to operation： transplantation group was （10±d） days, control group was （9±6） days. SV, FS, LVEF, LVEDs improved significantly at the follow-up of the forty-fifth, ninetieth day in the two groups （P〈0.05）, but transplantation group was better than control group. LVEDd in transplantation group at the ninetieth day was better than that in control group （P〈0.05）. S, E, A maximum value which reflect local systolic and diastolic functions of heart also improved significantly at some spots of bicuspid valve ring in the two groups at the forty-fifth, ninetieth day （P〈0.05） , and transplantation group was better than control group （P〈0.05）. LVEDd and A maximum value in control group got bigger at the ninetieth day than those before operation （P〈0.05） （heart remodeling）, but in transplantation group their changes was unconspicuous between before and after operation （P〉0.05）. VEGF-Ab＇s concentration （pg/ml） in transplantation group was much higher than that in control group at the fifth, forty-fifth, ninetieth day （P〈0.05）. Conclusions Intra-coronary ABM-MNCs transplantation can effectively improve systolic and diastolic functions of AMI heart as well as inhibit AMI heart from remodeling. High VEGF expressing may be relative with stem cell transplantation, and may be a mechanism that stem cells are good for AMI.