组织多普勒超声心动图评价心肌病兔骨髓基质细胞移植后的心肌功能(英文)

Evaluating myocardial function of a cardiomyopathy rabbit model following bone marrow stromal cell transplantation by tissue Doppler echocardiography

背景:组织多普勒超声心动图被证明可以用来评价心脏的整体和局部功能,但用于评价骨髓基质细胞移植对阿霉素所致兔心肌病的连续观察研究较少。目的:利用组织多普勒超声心动图评价骨髓基质细胞直接注射治疗阿霉素所致心肌病心肌功能的变化。设计、时间及地点:随机对照动物实验,于2002-09/2003-12在华中科技大学同济医学院附属协和医院超声科实验室完成。材料:雄性成年日本大耳白兔28只,体质量(2.0±0.2)kg,利用阿霉素诱导其中20只制备扩张型心肌病模型。方法:造模成功后,20只白兔分为细胞移植组和PBS组,每组10只。8只生理盐水处理组作为假手术组。细胞移植组于实验开始第8周每只兔分别取其骨髓进行骨髓基质细胞培养。第12周进行细胞荧光标记后,于心外膜直接注射回各自兔的左室侧壁心肌处。PBS组于第12周注射相同剂量的PBS培养液作为对照。另外8只作为假手术组仅开胸,每次给予相同剂量生理盐水。主要观察指标:细胞移植前及移植后4周利用常规和组织多普勒超声心动图评价左室整体和局部功能;组织学和荧光检测观察心肌细胞形态变化。结果:①细胞移植组组织多普勒发现局部注射区组织速度增高,由(4.0±1.1)cm/s到(5.3±1.2)cm/s(P<0.05),而整体功能未见明显改善。PBS组及假手术组整体和局部心肌功能均未见改善。②细胞移植后4周存活的细胞仍可见DAPI荧光标记。组织学检查发现注射区附近心肌损伤减轻,凋亡较少。结论:骨髓基质细胞治疗扩张型心肌病可以改善局部心肌功能,组织多普勒可以检测出局部心肌功能的改善,为细胞移植提供了一种有效的评价手段。

BACKGROUND： Tissue Doppler echocardiography （TDE） has been proved to evaluate general and local function of heart but less reported on adriamycin-induced cardiomyopathy following bone marrow stromal cell （BMS） transplantation. OBJECTIVE： To evaluate myocardial function of an addamycin-induced cardiomyopathy rabbit model following BMS transplantation using TDE. DESIGN, TIME AND SETTING： A randomized animal control study was performed at Laboratory of Ultrasound, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from September 2002 to December 2003. MATERIALS： A total of 28 male adult Japanese rabbits weighing （2.0±0.2） kg were used in this study. Adriamycin was used to induce cardiomyopathy model in 20 rabbits. METHODS： Twenty-eight male Japanese rabbits were randomly divided into three groups： cell transplantation group （n=10）, PBS group （n=10）, and sham operation group （n=8）. BMSs were isolated from cell transplantation group at the 8th day. On the 12m week, cells were labeled with 4, 6-diamidino-2-phenylindole （DAPI）, and then epicardial directly injected into the myocardium of the same rabbits in thoracotomy surgery. Non-cell only culture fluid PBS was injected in PBS group. Sham operation group underwent thoracotomy surgery with the same volume of saline injection. MAIN OUTCOME MEASURES： Left ventricular function was assessed by conventional and tissue Doppler echocardiography before and 4 weeks after surgery. Histological examination including apotisis study and DAPI fluorescent were assessed after sacrificed. RESULTS： （1） In cell transplantation group, tissue Doppler echocardiography found the improvement of local tissue velocity from （4.0±1.1 ） cm/s to （5.3±1.2） cm/s （P 〈 0.05） around the inject site, but the improvement of global myocardial function was not found by conventional echocardiography. In PBS and sham operation group there were no differences in global and regional myocardial function changes before and after surgery. （2） Viable cells labeled with DAPI could be identified in myocardium at 4 weeks after transplantation. Histological findings showed that the injury of the myocardium around the injection site was relieved with less apoptosis. CONCLUSION： BMS cells transplantation for dilated cardiomyopathy is feasible and can improve regional left ventricular function, while tissue Doppler echocardiography can detect this regional myocardial function improvement, which could provide helpful information on the efficacy of cellular transplantation therapy.