Keap1-Nrf2信号在调节内皮祖细胞抗氧化和修复梗死心肌组织中的作用

Myocardial infarction reperfusion injures and heart failure progresses after infarction are both closely related to oxidative stress. Endothelial progenitor cells (EPC) has strong antioxidant capacity and play an important role in restoring heart function after myocardial infarction. However, some coronary heart disease injure factor, such as ox-LDL and AngⅡ, could still induce EPCs oxidative stress. But their mechanisms have not been fully illustrated. Keap1-Nrf2 is a very important endogenous anti-oxidation pathway. It regulates expression of a series of antioxidase. We think that ox-LDL and AngⅡ might inhibit EPC anti-oxidation system and impair EPC repairing ischemic heart capacity via inhibiting keap1-Nrf2 signal. This project intends to firstly investigate the effect of ox-LDL and AngⅡ on keap1-Nrf2 signal and its regulating molecules via Western blot and specific inhibitor, secondly investigate the role of keap1-Nrf2 signal in regulating of EPCs function and capacity of repairing ischemic heart via up-regulation and down-regulation keap1-Nrf2 signal with siRNA, finally provide a new theory to improve EPC repairing infarcted myocardial tissue.

心肌梗死再灌注损伤和梗死后心衰进展与氧化应激密切相关。内皮祖细胞（EPC）具有较强抗氧化能力，在心肌梗死后心功能的恢复中发挥重要作用。但一些冠心病损伤因子，如氧化低密度脂蛋白(ox-LDL)、血管紧张素Ⅱ(AngⅡ)仍可导致EPC出现氧化应激反应，而机制不是十分清楚。Keap1-Nrf2 是一条重要的内源性抗氧化应激通路，能够调控一系列重要的抗氧化酶。我们认为ox-LDL和AngⅡ可能通过抑制Keap1-Nrf2，抑制EPCs的抗氧化系统，从而损害EPC对缺血心脏的修复作用。本项目首先通过免疫印迹和特异性阻断剂了解ox-LDL和AngⅡ对EPC Keap1-Nrf2信号的作用及其调控分子，其次通过siRNA干扰上调和下调Keap1-Nrf2信号了解其在EPC功能调节以及在修复缺血心脏中的作用，为改善EPC治疗梗死心肌的能力提供新的思路。