甘油醛－3－磷酸脱氢酶（GAPDH）参与心肌梗死后心肌保护和心脏重构的机制研究

项目名称： 甘油醛－3－磷酸脱氢酶（GAPDH）参与心肌梗死后心肌保护和心脏重构的机制研究

项目编号： No.31271525

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 姚玲玲

作者单位： 复旦大学

项目金额： 85万元

中文摘要： 在青年基金的资助下，发现气体分子H2S可在大鼠缺血再灌注损伤引发的心肌梗死模型中抑制心肌细胞的凋亡，在该项目实施过程中我们意外地发现一直作为内参分子的GAPDH的活性在H2S作用下有所升高，对其进一步研究发现转染了活性增强的GAPDH质粒的大鼠心肌细胞能够抗营养剥夺引发的凋亡，并且能够改善心脏重构；但目前尚无GAPDH分子对于心肌梗死和心肌梗死引发的心脏重构作用的相关报道，本项目分为两部分：1. 在大鼠心脏急性缺血损伤模型中，梗死局部心脏注射过表达活性GAPDH蛋白的病毒，研究GAPDH活性增强发挥的抗心肌梗死，改善心功能的作用机制；2. 在大鼠心肌梗死后心脏重构模型中，研究GAPDH活性增强对心肌代偿肥大期炎症反应和心脏重构的影响及其作用的分子信号机制。力图明确GAPDH活性增强对细胞凋亡、炎症反应、心脏重构等一系列的影响，阐明其分子机制，为寻找新型治疗心肌梗死药物开创新思路。

中文关键词： 心肌梗死；3-磷酸甘油醛脱氢酶；线粒体；活性氧；凋亡

英文摘要： With the financial aid of the Yong Project of NSFC, we investigated the mechanism of gaseous molecular H2S protected rat neonatal cardiomyocytes from apoptosis ,and in the investigation, we surprised to observed that GAPDH, the "house keeping" protein, its activity increased under H2S treatment. With more investigation, we found that GAPDH activity increase could prevent cardiomyocytes from apoptosis and improved the cardiac reconstruction- induced by heart infarction. However, little report has been seen to investigate the role of GAPDH in cardiac infarction、inflammation and reconstruction. In this project, two mainly contents were investigated: 1. In the rat heart left anterior descending coronary artery (LAD) ligation-induced infarction modle, to investigate the role of GAPDH activity in preventing cardiomyocytes apoptosis and improving the cardiac function; 2. In the rat heart reconstruction models which are induced by LAD ligation, to investigate the role of GAPDH activity in inflammation and improving the cardiac reconstruction. To verify the function of GAPDH activity increase on cell apoptosis、inflammation and reconstruction, to clarify the mechanism and to provide a new idea to treat heart infarction.

英文关键词： infarction；GAPDH；ROS；mitochondrial；apoptosis