TWEAK/Fn-14介导的氧化应激在冠状动脉微栓塞后心肌原肌球蛋白氧化修饰中的作用和机制

项目名称： TWEAK/Fn-14介导的氧化应激在冠状动脉微栓塞后心肌原肌球蛋白氧化修饰中的作用和机制

项目编号： No.81200146

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 陈章炜

作者单位： 复旦大学

项目金额： 23万元

中文摘要： 冠状动脉微栓塞所致的围手术期心肌损伤严重影响冠状动脉介入治疗的预后。我们前期研究证实，肿瘤坏死因子α（TNF-α）参与了微栓塞后的心肌损伤，但是拮抗TNF-α受体没能完全改善心功能不全。作为TNF家族的另一个多功能因子- - 肿瘤坏死因子样凋亡弱诱导因子（TWEAK），是否参与微栓塞后的心肌损害尚不明确。我们前期实验发现小型猪冠脉微栓塞后心肌和血清的TWEAK水平升高，提示TWEAK可能参与心肌损伤。本课题拟通过建立小鼠冠脉微栓塞模型和心肌细胞TWEAK体外干预的方法，探究TWEAK及其受体Fn14在微栓塞后心肌损伤中的机制；重点研究TWEAK-Fn14介导的氧化应激对心肌原肌球蛋白的氧化修饰，应用质谱分析原肌球蛋白的氧化修饰位点及类型，探索抗氧化剂对上述氧化修饰的逆转作用；同时随访围手术期心肌损伤患者血清TWEAK和心血管预后的关系，为早期诊断、预防和治疗冠状动脉微栓塞提供理论依据。

中文关键词： 冠状动脉；微栓塞；氧化应激；肿瘤坏死因子样凋亡弱诱导因子；原肌球蛋白

英文摘要： Periprocedural myocardial injury caused by coromary microembolization greatly influence the clinical prognosis of coronary intervention. Our previous study documented that TNF-α was involved in the cardiac dysfunction after coronary microembolization. However, TNF-α receptor antaganism could not completely ameliorate cardiac dysfunction. As a member of of TNF superfamily, the effect of TWEAK on myocardial injury after coronary microembolization is unclear. Our previous work has demonstrated that TWEAK expression was enhanced after coronary microembolization, which implicated that TWEAK might participate in the cardiac dysfunction. This study is designed to clarify the mechanism of TWEAK/Fn14 in the myocardial injury after coronary embolization. Oxidative modification of cardiac tropomyosin mediated by TWEAK/Fn14-induced oxidative stress after coronary microembolization will be specially analyzed by mass spectrometry. Oxidative type and amino acid domain will be detected at the same time.In addition, in order to find the effective therapy method to cardiac dysfunction, the effect of antioxidant after coronary microembolization will be analyzed. Furthermore, we will explore the association of TWEAK and cardial prognosis after periprocedural myocardial injury in clinical study. These foundings could provide great s

英文关键词： coronary；microembolization；oxidative stress；TWEAK；tropomyosin