中文摘要
诱导性多能干细胞(iPSCs)是目前最为理想的心肌修复的候选细胞之一。有报道中药丹参提取物能够激活干细胞修复心肌的CXCR4信号通路,然而丹参的化学成分复杂,活性成分不清。我们前期研究表明,在各种丹参单体化合物中,丹参酚酸B具有明显的促进iPSCs修复急性心肌梗死后坏死心肌的作用,且提高体外培养的iPSCs的生物学特性,提高多向分化潜能性相关基因的表达,其机制与CXCR4下游信号通路Akt激活有关。因此,我们推测该信号通路在丹参酚酸B增强iPSCs修复急性心肌梗死后坏死心肌中可能发挥较关键的作用。本项目拟分别以H9C2心肌细胞及CXCR4配体SDF-1α基因敲除大鼠的心肌梗死模型为研究对象,探讨丹参酚酸B促进iPSCs细胞动员、归巢及分化的效果及分子机制,以阐明CXCR4-PI3K/Akt信号通路在其心肌修复过程中的角色,该研究将为丹参酚酸B用于iPSCs移植修复心肌提供理论依据。
英文摘要
Induced pluripotentstem cells is one kind of ideal candidate cells for repair of myocardium cells. Recent report showed Chinese medicine salvia miltiorrhiza extract could enhance the ability of stem cells to repair CXCR4 signal pathway. While the chemical component of salvia miltiorrhiza is complicated and active ingredients is not clear till now. Our earlier study showed among all the monomeric compound, Salvianolic acid B could improve the effect of myocardial infarction repair of iPSCs and the biological function of iPSCs significantly and enhance its expression of multi-directional differentiation potential genes. The mechanism might be related with Akt activation which is downstream signal of CXCR4. Thus, we suggest this signal pathway might play one key role in the repair of myocardium cells by iPSCs pretreated with Salvianolic acid B. In this study, we will discuss the effect of Salvianolic acid B pretreatment on iPSCs-CXCR4 gene expression and its possible downstream signal pathway. The H9C2 cells and myocardial infarction of CXCR4-ligand-SDF-1α gene knock-out rat will be focused to explore the effects of iPSCs' migration,homing and differentiation and the role of CXCR4-PI3K/Akt signal in biological function of improvement of iPSCs pretreated with Salvianolic acid B. It will support more theory evidence for myocardial cells repair of iPSCs.
