CGRP调节NF-κB信号通道促进心肌梗死后c-kit+心脏干细胞存活及分化的研究

心肌梗死后的心脏修复治疗是临床亟待解决的重大问题。多项研究提示，成年哺乳动物心脏中含有未分化的c-kit+心脏干细胞（c-kit+CSCs），对其激活及利用有助于梗死后心脏修复。然而梗死局部炎症和氧化应激的微环境，导致细胞利用率极低。我们既往研究显示RAMP1可上调CGRP的效应性，抑制NF-κB信号通路，从而改善梗死区域的炎症微环境。结合预实验结果，我们推测:CGRP可能具有增强内源性CSCs抵御局部微环境能力并促进细胞存活及分化。为验证此假设，本项目建立体外细胞氧化应激和大鼠心肌梗死模型，从不同角度观察CGRP对心肌梗死后氧化应激状态下c-kit+CSCs的存活及分化能力的影响，并检测此过程中NF-κB 相关信号蛋白和凋亡相关基因的表达水平，研究CGRP对CSCs的存活及分化的调节作用及其与微环境中NF-κB信号通道的关系，以期为提高干细胞移植治疗效果提供新的思路。

Myocardial infarction, one of the severe ischemic diseases, has few great progress in the therapy on improving cardiac function. Recently most studies have demonstrated that the adult mammalian heart contains a population of undifferentiated c-kitpos Linneg cells(c-kitpos CSCs), which are self-renewing, clonogenic ,and multipotent, giving rise to restore the infarted myocardium. However, the local microenvironment after myocardial infarction, including oxygen stress and inflammation, can lead to the transplanted or migrated cell undergoing apoptosis, making the utilization of transplanted or migration cell very low. NF-κB signaling pathway plays a key role in regulating the inflammatory microenvironment and apoptosis after myocardial infarction. Our previous study indicated CGRP can improve cardiac function after myocardial infarction by inhibiting NF-κB activation. Thus, we attempts to investigate whether CGRP can improve the survival and differentiation of CSCs after myocardial infarction by regulating NF-κB signaling pathway. In order to confirm this hypothesis, we study the effects of CGRP on CSCs survival and differentiation both on cell oxidative stress model in vitro and myocardial infarction model in vivo. Our experiment on correlations between NF-κB and CGRP is to reveal the mechanisms as well as accumulate experimental evidence and provide new methods for clinical stem cell therapeutics in myocardial infarction.