内质网应激在房颤伴发的细胞凋亡中作用及调节机制的研究

项目名称： 内质网应激在房颤伴发的细胞凋亡中作用及调节机制的研究

项目编号： No.81470455

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： 陈明龙

作者单位： 南京医科大学

项目金额： 73万元

中文摘要： 既往研究及本课题组前期的实验证实，心肌细胞凋亡对于心房颤动的预测、发生发展和转归有重要意义。内质网应激（ER stress）与凋亡的调控密切相关。然而，ER stress是否参与调控房颤病程中的细胞凋亡及其具体的下游调控机制目前未被清楚阐明。 先前的研究中，我们已成功建立房颤的细胞及动物模型，并在模型中观察到加剧的细胞凋亡现象。本课题在此基础上拟探讨：1.房颤伴发的心肌细胞凋亡中，是否有ER stress的发生，及其对凋亡的调控作用；2.探索ER stress是否通过激活线粒体损伤反应、MAPKs通路和细胞自噬进而调控凋亡，及激活通路；3.对ER stress的潜在下游靶点予以体内实验干预，验证其是否缓解细胞凋亡，进而减少房颤的发生。 本课题希望明确ER stress在房颤伴发的细胞凋亡中作用及调节机制，以期为房颤药物治疗的靶点选择提供新的思路。

中文关键词： 心房颤动；心肌细胞凋亡；内质网应激；信号通路

英文摘要： Accumulating evidences and our preliminary work have proven that cardiomyocyte apotosis is significantly related to prediction, occurrence, development and prognosis of atrial fibrillation(AF) which is the most common arrhythmia in clinical practice. Endoplasmic Reticulum Stress (ER stress) is one of the most important regulatory pathways in apotosis, while whether it is associated with apotosis accompanied by AF and its specific downstream molecular mechanisms has not been fully understood. In our previous study, animal model and cell model of AF had been successfully established and accelerated apotosis had been oberseved in both of these models. On this basis, we intend to: 1.investigate whether ER stress involves in regulating apotosis in AF and its regulatory effect. 2. explore the potential downstream molecular mechanisms（mitochondria， MAPKs pathway, autophagy） of ER stress that induce apotosis directly. 3. comfirm whether intervention on potential downstream signal in vivo could relieve apotosis and reduce occurrence of AF. In conclusion, this proposal is designed to identify the function of ER stress in apotosis induced by AF and its possible regulatory mechanisms, trying to search the promising target for drug therapy of AF.

英文关键词： Atrial Fibrillation;Cardiomyocyte Apotosis;ER stress;Signaling Pathway