新近研究发现，色素上皮衍生因子(PEDF)与心肌梗死(MI)后抗氧化应激作用密切相关，申请者前期预实验发现抗氧化蛋白金属硫蛋白2A(MT2A)是PEDF在心肌细胞的特异性结合分子。然而，MI后心肌细胞内是否存在PEDF-MT2A分子通路发挥抗氧化应激作用及其机制尚不清楚。本项目拟在前期研究的基础上，采用心脏条件性基因敲除小鼠(PEDF-cKO和MT2A-cKO)、双基因敲除小鼠(PEDF/MT2A-dcKO)，从整体和细胞水平研究心肌低氧性损伤后PEDF-MT2A信号通路抗氧化应激的功能及其分子信号机制，其研究成果将可能成为心脏氧化应激干预的新着眼点，为临床MI后氧化应激的防治提供新的理论基础和实验依据。

Recent studies have found that the pigment epithelium derived factor (PEDF) is closely related to antioxidative stress after myocardial infarction (MI). We have previously demonstrated that metallothionein 2A (MT2A) was a specific binding molecule of PEDF on cardiomyocytes. The existence of PEDF-MT2A molecular pathways play a role of resistance to oxidative stress after MI and the mechanism in myocardial cells is not clear. Based on our previous research, the cardiac-conditional knock-out mice (PEDF-cKO and MT2A-cKO) and double cardiac-conditional knock-out mice (PEDF/MT2A-dcKO) were used, this proposal is to investigate the anti-oxidative function of PEDF-MT2A in MI and cardiomyocytes, and to determine the molecular mechanism of PEDF-MT2A signaling in mediating cardiac oxidative stress. The outcome of this proposal could be a new therapeutic strategy in future treatment of cardiac oxidative stress, and provide a novel theory and experimental basis for prevention of MI oxidative stress.