项目名称： CD40配体加重内皮损伤介导的炎症反应及其在主动脉瘤发病与进展中的作用机制研究

项目编号： No.81470580

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： 张宏家

作者单位： 首都医科大学

项目金额： 75万元

中文摘要： 内皮细胞损伤介导的炎症反应是促使主动脉瘤发病的重要病理机制。本课题前期研究发现：通过药物阻止血小板活化与聚集可以抑制主动脉瘤发病，但血小板促使主动脉瘤发病的机制尚不明确。已有研究证实CD40L是血小板释放的重要炎症因子，其可以抑制内皮祖细胞功能，阻止内皮损伤修复。据此，本研究提出假设：CD40L可以通过抑制内皮祖细胞功能，加重内皮损伤介导的炎症反应，促使主动脉瘤的发病及进展。本研究拟在血管紧张素II诱导的主动脉瘤模型上，采用CD40L基因敲除小鼠，利用病理分析、免疫组化、细胞粘附、迁移等体内、体外实验技术，观察CD40L对主动脉瘤发病、血管内皮损伤、氧化应激、炎症反应、内皮祖细胞功能的作用，同时结合临床样本分析、随访研究，阐明CD40L与人主动脉瘤发病及进展的关系作用，从而明确CD40L通过加重内皮损伤介导的炎症反应，促使主动脉瘤发病及进展的作用及机制，以期为主动瘤的临床治疗提供新靶点。

中文关键词： 主动脉瘤；炎症反应；CD40配体

英文摘要： Inflammation mediated by endothelial cell injury is a key mechanism for aortic aneurysm formation. Our previous studies have shown that inhibition of platelet activition and aggregation with pharmacotherapy could prevent the development of aortic aneurysm. However, the initiators of the platelet activition and aortic aneurysm progression have not been clearly defined.Recent studies have demonstrated that CD40 ligand is an important inflammatory cytokine released by platelets.It could impair the function of endothelial progenitor cells and inhibit endothelial healing after arterial injury. Based on these findings, we hypothesized that CD4O ligand may play an important role via mechanisms such as influencing the function of endothelial progenitor cells and promoting inflammation mediated by endothelial cell injury. We will use angiotensin II induced aortic aneurysm mice model constructed on CD40 ligand knock out mice and human aortic aneurysm samples in this study. The experimental techniques involving include pathology staining, immunohistochemistry,cells adhension and transmigration both in vivo and in vitro. With human aortic aneurysm samples, we will define the relationship between CD40 ligand and aortic aneurysm formation in human. We seek to verify the mechanism and the role played by CD40 ligand in the development of aortic aneurysm, and provide a new target for clinical treatment of aortic aneurysm.

英文关键词： aortic aneurysm;inflammation;CD40 ligand