兔骨髓间充质干细胞自体移植对扩张型心肌病左心室功能的影响

Effects of autologous marrow mesenchymal cells transplantation on cardiac function in rabbits with adriamycin-induced cardiomyopathy

目的观察自体骨髓间充质干细胞(MSCs)移植对扩张型心肌病(DCM)兔的心脏形态大小、功能及脑钠肽(BNP)的影响。方法26只健康大耳白兔随机分为细胞移植组和DCM对照组,经兔耳缘静脉注射盐酸阿霉素建立DCM模型后,移植组移植MSCs[1×106],DCM对照组注射DMEM/F12培养基。于用药前、移植前和移植后4周采用超声心动图测量二组动物的心脏形态大小和心功能,酶联免疫吸附试验测定血浆BNP水平。移植后4周左心导管测定血流动力学指标,免疫荧光检测移植区组织内存活的移植细胞。结果超声心动图检查证实MSCs移植后4周移植组左室腔内径较DCM对照组明显减小(P<0.05),射血分数(EF)增加并显著大于DCM对照组(P<0.01)。左心导管测压显示移植组左室收缩压较DCM对照组增高,舒张末期压显著降低(均P<0.01)。移植后4周移植组的血浆BNP水平显著下降(P<0.01),而DCM对照组无显著性改变。移植组组织切片可见5溴-2脱氧尿苷(BrdU)染色阳性细胞,另外还发现部分移植细胞分化为血管内皮细胞,DCM对照组未见BrdU染色阳性细胞。结论DCM兔心肌内注射MSCs能减轻阿霉素致DCM后左室腔扩大,有效改善DCM兔的心功能。

Objective To assess the effects of autologous bone marrow mesenchymal stem cells （MSCs） transplantation on cardiac size and function , and plasma brain natriuretic peptide （BNP） in adriamycin-induced dilated cardiomyopathic （DCM） rabbit. Methods 26 healthy rabbits were randomly divided into transplant group and control group, and adriamycin was injected through ear-border vein to produce DCM model. Bone marrow MSCs[1×10^6]were injected to the left ventricular free wall in the transplant group. The size and the cardiac function were measured by echocardiography before administration, before and 4 weeks after transplantation, and plasma BNP levels were determined by Enzyme-linked immunoadsordent assay（ELISA） at the same time. Indexes of hemodynamics were recorded and transplant cells were measured by immunofluorescence at 4 weeks after surgery. Results The left ventricular diameter of the transplant group was smaller than that of the control group. The left ventricular ejection fraction （LVEF） increased and were higher than that of the control group（P〈0. 01）. Left ventricular systolic pressure（LVSP） increased and left ventricle end- diastolic pressures （LVEDP） decreased significantly in the transplant group. Furthermore, plasma BNP levels in the transplant group decreased significantly at 4 weeks after transplantation（P〈0. 01 ）, while it remained unchanged in the control group. BrdU positive （green） cells were observed in tissue section of the transplant group, and were not found in the control group. Otherwise, small part of BrdU positive cells differentiated into vascular endothelial cells. Conclusions Bone marrow MSCs transplantation can ameliorate the left ventricle dilatation and improved cardiac function in rabbits with adriamycin induced cardiomyopathy.