GATA4基因修饰骨髓间充质干细胞对心肌梗死大鼠心功能的影响

目的: 研究锌指转录因子(GATA4)基因修饰骨髓间充质干细胞（MSCs）对心肌梗死大鼠心功能的影响，为进一步探讨其机制提供依据。方法: 构建GATA4-pEGFP基因质粒，体外分离培养大鼠MSCs，利用脂质体将质粒转染入MSCs。40只SD大鼠制备大鼠心肌梗死模型,于术后10 d测定心功能指标。将模型鼠随机分为MSCs 组和DMEM组，每组各20只。MSCs 组将GATA4-pEGFP基因修饰的MSCs植入心肌梗死后10 d大鼠心肌梗死区，DMEM组同时注射等体积无血清DMEM于心肌梗死区。移植注射后4周，检测左心室射血分数（LEVF）和左室缩短分数（FS）。结果: 体外分离培养的MSCs呈梭形或条形，贴壁生长 。 GATA4-pEGFP重组基因质粒转染MSCs 2周后，可见细胞中有绿色荧光蛋白表达。移植4周后，MSCs组大鼠LEVF（85%±7%）明显高于DMEM组(47%±4%)（P<0.01）； MSCs组大鼠FS(52%±6%)明显高于DMEM组(35%±8%)（P<0.01）。结论: GATA4基因修饰的MSCs移植能够改善心肌梗死大鼠心功能。

Effect of mesenchymal stem cells modified by GATA4 on heart function in rats with myocardial infarction

Objective To investigate the effect of mesenchymal stem cells(MSCs) modified by GATA4-pEGFP gene on heart function in myocardial infarction rats and to provide basis for further research on its mechanism.Methods The MSCs were isolated and cultured in vitro.GATA4-pEGFP plasmid was constructed and transfected into MSCs by liposome.40 SD rats were operated to prepare myocardial infarction models and the heart function indexes of the models were evaluated 10 d after the operation.The model rats were randomly divided into MSCs group(n=20) and DMEM group(n=20).The MSCs modified by GATA4-pEGFP gene was transplanted into the area of myocardial infarction of rats 10 d after infarction in MSCs group.The equal volume of serum-free DMEM was injected into the myocardial infarction area of rats at the same time in DMEM group.The left ventricular ejection fraction(LVEF) and fractional shortening(FS) 4 weeks after injecting were detected.Results The isolated MSCs in vitro adhered to the plate and they presented fusiform or spindle shape.2 weeks after transfection with recombinant gene plasmid GATA4-pEGFP,the green fluorescence protein expressed in MSCs.4 weeks after transplantation,the LEVF value in MSCs group(85%±7%) was increased significantly compared with DMEM group(47%±4%)(P<0.01),and the FS value in MSCs group(52%±6%) was also increased significantly compared with DMEM group(35%±8%)(P<0.01).Conclusion The heart function of myocardial infarction rat can be improved by transplanting MSCs modified by GATA4 gene.