MMSCs移植对大鼠心肌梗死后MMP-2,TIMP-2表达及心室重构的影响

Effects of marrow mesenchymal stem cells on expression of MMP-2 and TIMP-2 in rats ventricular remodeling after myocardial infarction

目的:研究骨髓间充质干细胞(MMSCs)移植对实验性心肌梗死(MI)大鼠心肌细胞外基质金属蛋白酶(MMP-2)和基质金属蛋白酶抑制剂(TIMP-2)的表达及心室重构的影响.方法:采用开胸结扎冠状动脉左前降支(LAD)的方法制作MI大鼠模型,造模成功后12～14d经大鼠舌下静脉移植已转染增强型绿色荧光蛋白(pEGFP-C1)的MMSCs,分4,8wk2个时段检测大鼠左心及全心质量指数、胶原含量及MMP-2,TIMP-2的量效变化,荧光显微镜观察绿色荧光的表达.结果:4wk时移植组左心质量指数为[(1.69×10-3)±(11.02×10-5)],全心质量指数为[(2.22×10-3)±(5.08×10-5)]均较同期模型组[(1.83×10-3)±(9.48×10-5)],[(2.47×10-3)±(17.16×10-5]显著降低(P<0.01).8wk时其变化趋势与4wk时相同.4wk时移植组的胶原含量为(11.19±1.15)%较同期模型组的胶原含量(27.89±5.59)%显著降低(P<0.01),8wk时变化趋势与4wk时相同.移植组MMP-2的表达显著低于同期模型组中MMP-2的表达,而TIMP-2的表达在同期移植组与模型组间未见明显差异.结论:MMSCs移植可较为有效地改善大鼠实验性MI后的心室重构,其作用可能与降低心肌组织中MMP-2的表达有关,而非增加TIMP-2的表达.

AIM：To investigate the effect stability after transplantation marrow mesenchymal stem cells（MMSCs）tagged pEGFP-C1 plasmid to MI models 4 and 8 weeks.METHODS：Myocardial infarction was operated by ligation of the left anterior descending coronary artery（LAD）in adult SD rats.Four and 8 weeks after MMSCs implantation,left ventricular weight and body weight ratio and heart weight and body weight ratio were determined.Van Gieson staining was used for measurements and calculation of the myocardial fibers collagen.And MMP-2 and TIMP-2 expression were detected.Then we investigated the migration and evolution of MMSCs in vivo by fluorescent microscope.RESULTS：First of all,the numbers of left ventricular weight and body weight ratio[（1.69×10^-3）±（11.02×10^-5）]and heart weight and body weight ratio[（2.22×10^-3）±（5.08×10^-5）]were significantly decreased（P〈0.01）compared with the numbers[（1.83×10^-3±9.48×10^-5）]and[（2.47×10^-3）±（17.16×10^-5）]after transplantation MMSCs 4 weeks.Then the number of ratio was significantly decreased after transplantation MMSCs 8 weeks.Secondly,the numbers of myocardial fibers collagen（11.19±1.15）% was significantly reduced（P〈0.01）compared with the numbers（27.89±5.59）% after transplantation MMSCs 4 weeks.Then the number of myocardial fibers collagen was significantly decreased aftertransplantation MMSCs 8 weeks.Thirdly,the expressions of MMP-2 were dropped gradually.CONCLUSION：Transplanting MMSCs can improve the ventricular remodeling to acute MI rat models.This function depends on decreasing the numbers of MMP-2 instead of increasing the numbers of TIMP-2.