sRAGE对缺血/再灌注的心脏保护作用及其机制

项目名称： sRAGE对缺血/再灌注的心脏保护作用及其机制

项目编号： No.30801217

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 生物科学

项目作者： 郭彩霞

作者单位： 首都医科大学

项目金额： 26万元

中文摘要： 目的：研究sRAGE与心肌缺血/再灌注损伤的关系，探讨sRAGE心肌保护机制及信号转导途径，为临床防治冠心病提供新思路和方法。结果： ①/R动物和H/R心肌细胞sRAGE降低，外源性sRAGE提高H/R心肌细胞活力且降低LDH含量。②lucose可以提高内皮细胞培养基sRAGE水平。③RAGE降低H/R心肌细胞ROS和MDA含量，增强SOD活力；减轻线粒体膜电位去极化以及mPTP开放；降低凋亡率，下调bax和caspase-3；降低NO，减少eNOS；下调ERK表达，降低ERK及p38活性。④#24613;性心梗组sRAGE水平显著高于非心梗组和非冠心病组，sRAGE与冠心病严重程度相关；PCI术后NSTEMI组心功能改善和sRAGE增加百分数明显高于STEMI组。结论：①RAGE作用在心肌细胞拮抗心肌I/R损伤；内源性sRAGE下调可能是H/R损伤的机制之一。②RAGE通过影响氧化应激、线粒体mPTP开放和细胞凋亡发挥心脏保护作用；经NO/NOS、MAPK途径介导。③RAGE反映冠脉病变严重程度，可能为AMI预警信号；sRAGE增加水平与心功能改善有关。

中文关键词： sRAGE；缺血/再灌注损伤；mPTP；NO/NOS；MAPK

英文摘要： Objectives: To research relationship between level of plasma sRAGE and myocardial ischemia-reperfusion (I/R) injury. To explore the cardioprotection mechanism of sRAGE and expression of cellular signal transduction pathway. To provide new thought and method for prevention and treatment of coronary heart disease. Results: 1. Endogenous sRAGE level in animals with myocardial I/R damage and cardiomyocyte with H/R damage reduced. Exogenous sRAGE improved the vitality of H/R cardiomyocyte and reduced LDH level. 2. Glucose can improve sRAGE level in endothelial cells medium.3.Exogenous sRAGE reduced H/R cardiomyocyte damage, while it can reduce ROS in myocardium, MDA in medium and strengthen SOD activity. It can also relieve dapolarization of mitochondrial membrane potential and weaken opening of mitochondrial transmembrane potential (mPTP), reduce cardiomyocyte apoptosis and influence of H/R to bax, down-regulate caspase-3, reduce NO level of medium and eNOS, down-regulate ERK, and reduce activity of ERK and p38. 4. sRAGE level in acute myocardial infarction group was higher than that in coronary heart disease without acute myocardial infarction group and non-coronary heart disease group. Correlation existed between sRAGE level and severity of coronary heart disease. Degree of improvement of cardiac function and sRAGE level in NSTEMI group was significantly higher than that in STEMI group. Conclusion: 1.sRAGE antagonized myocardial I/R damage by cardiomyocyte. Down-regulation of endogenous sRAGE may be one of the mechanisms of H/R damage. 2. sRAGE protected heart through effecting oxidative stress, mitochondria MPTP open and apoptosis. This effect may be mediated by the NO/NOS and MAPK way. 3. sRAGE level reflected severity of coronary artery lesions , and may be a warning sign to AMI. Increasing level of plasma sRAGE was correlated with improving of cardiac function.

英文关键词： sRAGE;ischemia/reperfusion;mPTP; NO/NOS;MAPK