Gal-3在AGEs介导单核巨噬细胞生物学行为中的作用及机制

项目名称： Gal-3在AGEs介导单核巨噬细胞生物学行为中的作用及机制

项目编号： No.81500331

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 陈侃

作者单位： 上海交通大学

项目金额： 18万元

中文摘要： 糖尿病患者冠心病发病率显著高于普通人群，强化降糖治疗并不能显著降低糖尿病心血管并发症，提示除高血糖外，还有其他重要因素参与糖尿病致动脉粥样硬化的病理过程。糖尿病患者体内AGEs生成显著增加，AGEs与单核巨噬细胞表面受体结合后，可加速单核巨噬细胞吞噬脂质及泡沫化，并增加炎症因子的释放，从而促进动脉粥样硬化的进展。Gal-3在体内主要由单核巨噬细胞产生和分泌，且与AGEs有高亲和力，因此我们推测Gal-3可能在AGEs介导单核巨噬细胞生物学行为中起作用。本项目将首先进行体外实验，研究Gal-3在AGEs介导单核巨噬细胞生物学行为中的作用及其机制。在此基础上，使用斑马鱼为动物模型，通过体内实验验证体外实验的结果，并在整体水平上研究Gal-3对动脉粥样硬化形成发展的影响。本项目将为糖尿病性动脉粥样硬化的防治提供新的研究方向和干预靶点。

中文关键词： 动脉粥样硬化；糖尿病；晚期糖基化终末产物；单核巨噬细胞；半乳凝集素3

英文摘要： The incidence of coronary heart disease in diabetic patients is significantly higher than in the general population. Intensive blood–glucose control can not significantly reduce the cardiovascular complications of diabetes, suggesting that in addition to hyperglycaemia there are other important factors involved in the pathological process of diabetes inducing atherosclerosis. In the diabetic state, AGEs content in vivo rises. AGEs combine with the receptors in the membrane of mononuclear macrophages and change the behavior of mononuclear macrophages, which promotes the progress of atherosclerosis. Gal-3 is mainly produced and secreted by mononuclear macrophages in vivo and can integrate with AGES closely. Therefore, we speculate that Gal-3 may play some important roles in the process of AGEs mediating mononuclear macrophages behavior. In this project, we will firstly study the roles of Gal-3 in the process of AGEs mediating mononuclear macrophages behavior and its mechanisms in vitro. Then, we will use zebrafish as animal model and verify the results in vivo. We will also examine the effect of Gal-3 on the progress of atherosclerosis. This project will provide new research directions and intervention targets for atherosclerosis.

英文关键词： atherosclerosis;diabetes;advanced glycation end products;mononuclear macrophage;galectin-3