脂肪间充质干细胞移植治疗扩张型心肌病大鼠的研究

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目的脂肪间充质干细胞(ADMSCs)移植对扩张型心肌病(DCM)大鼠心肌损伤及心功能的影响。方法80只健康Wistar大鼠腹腔注射阿霉素建立DCM大鼠模型,按随机数字表法分为治疗组和对照组,各35只(建模中死亡5只,建模后又处死5只)。将体外分离培养的ADMSCs移植入治疗组DCM大鼠,同时将以相同体积的IMEM培养基移植入对照组DCM大鼠。术后4周,处死动物留取心脏,于荧光显微镜下观察ADMSCs植入后存活及分化情况。于细胞移植术前、术后4周,将两组大鼠进行超声心动图、血流动力学检查,测定、比较心功能的指标。结果①注药4周后,根据留取大鼠心脏的大体形态、病理切片及心功能指标,提示DCM大鼠模型建立成功。②移植术后4周,于移植部位可见DAPI标记的ADMSCs,同时,免疫组织荧光染色发现部分DAPI阳性细胞,TnT染色也为阳性,且排列方向与心肌细胞一致。③移植术后4周,对照组与ADMSCs治疗组比较,左心室舒张末容积(LVEDV)及左心室收缩末容积(LVESV)明显减少(P<0.01);左心室每搏量(SV)、心脏射血分数(EF)、左心室收缩压(LVSP)、左心室室内压最大上升/下降速率(±dp/dtmax)均明显增加(P<0.05,P<0.01)。结论ADMSCs移植可在心肌内存活,并可分化为心肌细胞,改善DCM大鼠的心脏功能。 Effects of Adipose-derived Mesenchymal Stem Cells Transplantation on Myocardial Injury and Heart Function in Dilated Cardiomyopathy Rats. Methods Totally 80 healthy Wistar rats were injected intraperitoneally with doxorubicin to establish a DCM rat model. The rats were randomly divided into treatment group (n = 35) and control group (n = 5) . ADMSCs cultured in vitro were transplanted into DCM rats in the treatment group, while DCM rats in the control group were transplanted with the same volume of IMEM culture medium. Four weeks after the operation, the animals were sacrificed and the hearts were sacrificed. The survival and differentiation of ADMSCs after implantation were observed under a fluorescence microscope. Before cell transplantation, 4 weeks after operation, the echocardiography and hemodynamics were performed on both groups to determine and compare the indexes of cardiac function. Results ① After 4 weeks of injection, according to the general morphology, pathological sections and cardiac function indexes of the rat heart, the rat model of DCM was established successfully. At 4 weeks after transplantation, DAPI-labeled ADMSCs were observed at the transplanted site. Meanwhile, some DAPI positive cells were found by immunofluorescence staining, and TnT staining was also positive. The alignment direction was consistent with that of cardiomyocytes. ③ At 4 weeks after transplantation, left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) decreased significantly in the control group compared with the ADMSCs group (P <0.01); left ventricular stroke volume EF, LVSP and ± dp / dtmax increased significantly (P <0.05, P <0.01). Conclusion ADMSCs transplantation can survive in the myocardium and can differentiate into cardiomyocytes and improve the cardiac function in DCM rats.
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