转化生长因子β1在大鼠骨髓间充质干细胞移植修复梗死心肌中的作用

背景：大量研究显示，骨髓间充质干细胞是通过旁分泌作用，促使移植部位大量肌纤维母细胞聚集，分泌大量胶原蛋白，从而使梗死后心脏得到有利修复，并改善心脏收缩舒张功能。目的：探讨转化生长因子β1在大鼠骨髓间充质干细胞修复梗死心肌过程中的作用。方法：①体外实验：模拟心肌梗死后微环境培养大鼠骨髓间充质干细胞，检测其分泌肿瘤坏死因子α、血小板衍生生长因子、转化生长因子β1浓度。②体内实验：将大鼠Brdu标记的骨髓间充质干细胞、转化生长因子β1、PBS分别移植到梗死后心肌内，免疫细胞化学染色、PCR、Wester-blot等方法检测移植后大鼠心肌胶原蛋白Ⅰ、Ⅲ形成的差异。结果与结论：心肌梗死后微环境下培养大鼠骨髓间充质干细胞14 d可检测到培养基内有高浓度转化生长因子β1。移植骨髓间充质干细胞、转化生长因子β1大鼠心肌部位可检测到肌纤维母细胞的聚集及胶原蛋白Ⅰ、Ⅲ表达。结果显示大鼠骨髓间充质干细胞移植梗死心肌后，可促进胶原蛋白Ⅰ、Ⅲ的生成，从而改善心脏收缩功能，其中骨髓间充质干细胞所分泌的转化生长因子β1可能发挥重要作用。

Role of transforming growth factor β1 during transplantation of rat bone marrow mesenchynmal stem cells for repair of myocardial infarction

BACKGROUND:Studies have demonstrated that bone marrow mesenchymal stem cells promote the accumulation of a large number of myofibroblasts in the site of transplantation by paracrine action, secrete much collagen, which contributes to repair of myocardial infaction and improvement of cardiac systolic and diastolic function.OBJECTIVE:To investigate the role of transforming growth factor β1 during transplantation of rat bone marrow mesenchynmal stem cells for repair of myocardial infarction.METHODS:(1) In vitro experiments: rat bone marrow mesenchymal stem cells were cultured in simulated micro-environment of myocardial infarction. The levels of tumor necrosis factor α, platelet derived growth factor, and transforming growth factor β1 were detected. (2) In vivo experiments: BrdU-labeled rat bone marrow mesenchymal stem cells, transforming growth factor β1 and PBS were transplanted into the infracted myocardium. The difference of collagen Ⅰ, Ⅲ expression in rat myocardium post-transplantation was determined by immunohistochemical staining, PCR, western blot methods.RESULTS AND CONCLUSION:After rat bone marrow mesenchymal stem cells were cultured in simulated micro-environment for 14 days, high level of transforming growth factor β1 could be detected. These findings suggest that transplantation of rat bone marrow mesenchymal stem cells into infarct myocardium can promote the generation of collagen Ⅰ, Ⅲ and improve rat cardiac systolic and diastolic function, and transforming growth factor β1 may play an important role.