PI3K/Akt/FoxO3a信号通路在FGF-2心肌保护效应中的作用研究

项目名称： PI3K/Akt/FoxO3a信号通路在FGF-2心肌保护效应中的作用研究

项目编号： No.81470435

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 姜志胜

作者单位： 南华大学

项目金额： 72万元

中文摘要： 成纤维细胞生长因子2 (FGF-2) 作为一种重要的内源性细胞保护因子，它可以显著对抗心肌缺血和缺血/再灌注损伤，改善心功能，其心肌保护作用与激活PKC及MAPK等细胞内信号转导通路相关。但FGF-2的心肌保护效应也难以完全用PKC、MAPK的激活来解释。本课题组近期发现FGF-2可拮抗心肌细胞的氧化应激损伤，并可增强氧化应激时心肌细胞中Akt的活性。这些结果提示FGF-2的心肌保护效应可能与PI3K/Akt通路有关。我们拟通过建立心肌细胞氧化应激损伤和心肌缺血/再灌注损伤模型，应用PI3K/Akt的特异性抑制剂，通过基因转染和免疫沉淀等分子生物学技术，探讨PI3K/Akt/FoxO3a信号通路在FGF-2拮抗心肌细胞氧化应激损伤和心肌缺血/再灌注损伤中的作用，探索FGF-2心肌保护效应的新机制和新靶点，并为相应的干预措施提供新策略。

中文关键词： 成纤维细胞生长因子2；心肌细胞；氧化应激损伤；缺氧复氧损伤；细胞内信号转导

英文摘要： As an important endogenous protective factor, FGF-2 can directly exert a protective role against myocardial ischemia/reperfusion injury,and improve cardiac function through PKC and MAPK activation. However, the cardiprotection by FGF-2 can not be explained completely by activation of PKCs and MAPKs,because of the diversity of PKC and MAPK subtypes and the inconsistencies of their subcategory features. Recently, we found that FGF-2 can stimulate the activity of Akt against oxidative stress-mediated injury in myocardial cell,which imply that the PI3K/Akt signaling pathway may be involved in the protective effect of FGF-2 . This study by establishing oxidative stress model of cardiac myocytes and myocardial ischemia/reperfusion, aims to observe the effects of oxidative stress on myocardial cells, through application of PI3K/Akt specific inhibitors and molecular biology techniques, such as gene transfection and immune precipitation, to explore the role of PI3K/Akt/FoxO3a signaling pathways in FGF-2-induced influence against oxidative stress injury and myocardial ischemia/reperfusion injury, and consequently, new targets involved in FGF-2 cardiprotection, and new strategies for intervention in injury caused by myocardial ischemia/reperfusion and oxidative stress are expected to be elucidated.

英文关键词： Fibroblast growth factor 2;Cardiomyocytes;oxidative stress injury;hypoxia/reoxygenation injury;intracellular signal transduction