c-Jun氨基末端激酶在内毒素血症心肌细胞内质网应激及自噬中的作用研究

项目名称： c-Jun氨基末端激酶在内毒素血症心肌细胞内质网应激及自噬中的作用研究

项目编号： No.81200176

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： 赵鹏

作者单位： 山东大学

项目金额： 23万元

中文摘要： 内毒素血症是机体对感染的系统性反应，目前针对内毒素血症造成的心肌细胞损伤的机制仍有许多方面尚未明确。目前已有的部分研究表明JNK（c-Jun氨基末端激酶）活化对内毒素血症小鼠心肌细胞具有一定的保护作用。基于课题组前期内毒素血症与内质网应激的理论研究基础，本项目拟以内毒素血症心肌细胞损伤的早期干预与治疗为研究目的，应用细胞系和转基因动物模型，探讨JNK在内毒素血症心肌细胞内质网应激和自噬中的作用机制。并进一步利用siRNA、染色质免疫沉淀 (ChIP) 等技术作为检测手段，从基因和蛋白水平两方面明确JNK下游转录因子c-Jun在调节心肌细胞自噬中的地位。本研究可深入了解内毒素血症心肌细胞损伤发生和发展的机制，不仅为寻求内毒素血症心肌细胞损伤的理想治疗靶点提供理论基础，而且为解决内毒素血症造成的多器官功能衰竭、降低临床死亡率提供相关科学依据。

中文关键词： c-jun；小鼠胚胎成纤维细胞；凋亡；巨噬细胞迁移抑制因子；钙调神经磷酸酶

英文摘要： Endotoxemia is a systemic response of organism to infection. Many aspects of the mechanism aiming at the endotoxemia caused by myocardial cell injury are not clear yet. At present, part of the study showed that the JNK ( c-Jun N-terminal kinase ) activation has protective effect on myocardial cell in endotoxemic mice. Based on the early study on endotoxemia and endoplasmic reticulum stress theory of the research group, this project aims at the early intervention and treatment of Lipopolysaccharide-induced cardiomytes using cell lines and transgenic animal model and discusses the affecting mechanism of JNK in lipopolysaccharide-induced cardiomytes ER stress and autophagy. And further make clear the position of JNK downstream of the transcription factor c-Jun in the regulation of autophagy from two aspects of the gene and protein levels the use of siRNA and chromatin immunoprecipitation ( ChIP ) technology. This study can be a thorough understanding of occurrence and development mechanism of endotoxemia in myocardial cell injury. It not only provide theoretical basis for looking for the ideal therapeutic target of lipopolysaccharide-induced cardiomytes injury but also provide scientific basis for solving multiple organ failure caused by endotoxemia myocardial cell injury and reduce clinical mortality.

英文关键词： c-jun；mouse fibroblasts；apoptosis；macrophage migration inhibitory factor；calcineurin