脂肪间充质干细胞移植治疗兔急性心肌梗死的实验

Transplantation of adipose tissue-derived mesenchymal stem cells for the therapy of acute myocardial infarction in rabbits

目的:研究脂肪间充质干细胞(adipose tissue-derived mesenchymal stem cells,ADMSCs)移植治疗兔急性心肌梗死的效果及可能机制。方法:将30只兔随机分为假手术组、模型组及移植组,每组10只。模型组及移植组兔结扎冠状动脉左前降支建立急性心肌梗死模型,移植组在急性心肌梗死1 h内将DAPI标记的ADMSCs植入梗死区数个不同部位。术后4周行超声心动图检查兔心功能变化;处死动物测量左室质量指数,进行组织学观察,采用免疫荧光方法鉴定移植的细胞;利用RT-PCR及Western blot检测心肌组织中转化生长因子-β1(TGF-β1)、结缔组织生长因子(CTGF)和基质金属蛋白酶-1(MMP-1)的表达。结果 :移植组心肌组织切片中可见DAPI标记的细胞;移植后4周,与模型组相比,移植组心功能明显改善,梗死区微血管密度显著升高;移植组心肌组织TGF-β1和CTGF的表达水平均较模型组明显降低,MMP-1表达水平较模型组明显增加。结论:ADMSCs移植除了自身分化为心肌样细胞修补梗死心肌外,还可通过影响TGF-β1、CTGF和MMP-1表达,抑制心室重构,改善心功能。

Objective： To investigate the effects of adipose tissue-derived mesenchymal stem cells （ADMSCs） transplantation in acute myocardial infracted （AMI） model of rabbits and possible mechanisms. Methods： A total of 30 Japanese big ear albino rabbits were randomly divided into three groups： sham-operation group, model group and transplantation group. The left anterior descending （LAD） arteries of rabbits in modell group and transplantation group were ligated to establish models of AMI. Then in transplantation group, DAPI-marked ADMSCs were transplanted into different parts of the infarct zone in the first one hour. Echocardiography was used to evaluate cardiac function changes in rabbits at the fourth week after operation. After rabbits sacrificed, left ventricular mass index and histological changes were measured and identification of transplanted cells was carried out by using immunofluorescence. Besides, RT-PCR and Western blot were used to detect the mRNA and protein levels of transforming growth factor-β1 （TGF-β1）, connective tissue growth factor （CTGF） and matrix metalloproteinase-1 （MMP-1）. Results： The DAPI labeled cells were observed in myocardial biopsy in transplantation group. Compared with the model group, cardiac function and mierovessel density in transplantation group increased significantly in the fourth week after transplantation. The mRNA and protein levels of TGF-β1 and CTGF in the myocardial tissue of transplantation group were significantly lower than those of model group, but the levels of MMP-1 in myoeardium of transplantation group were statistically higher than those in model group. Conclusion： ADMSCs transplantation can not only differentiate into cardiomyocyte-like cells alleviating myocardial infarction, but also inhibit left ventricular remodeling and improve heart function possibly by effecting the expression of TGF-β1, CTGF and MMP-1.