Ly-6Chi单核细胞分化的调控及其致动脉粥样硬化机制的探讨

项目名称： Ly-6Chi单核细胞分化的调控及其致动脉粥样硬化机制的探讨

项目编号： No.81200199

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： 张大庆

作者单位： 中国医科大学

项目金额： 23万元

中文摘要： 动脉粥样硬化性疾病是目前危害人类健康的主要疾病，单核巨噬细胞是其病变的核心成分。目前研究显示单核细胞具有异质性，而且该现象普遍存在于鼠和人类。我们和他人最新研究证明动脉粥样硬化的多个危险因素可促进Ly-6Chi单核细胞亚群的分化、并与其加速动脉粥样硬化病变密切相关。但关于Ly-6Chi单核细胞亚群如何致动脉粥样硬化，及其分化的调控机制目前尚不清楚。本研究将利用动脉粥样硬化易感模型，探讨各单核细胞亚群在动脉壁内分化成巨噬细胞的能力；明确各单核细胞亚群参与炎症反应和进入动脉内皮下能力的区别；检测有关参与Ly-6Chi单核细胞亚群分化的调控机制、寻找可能的干预环节；并在人群中评估单核细胞亚群与冠状动脉粥样硬化斑块易损性的关系，为动脉粥样硬化性心血管疾病的防治开辟新的思路。

中文关键词： 动脉粥样硬化；炎症性单核细胞；普罗布考；同型半胱氨酸；氧化应激

英文摘要： Atherosclerotic disease is a kind of life-threatening disease. Monocyte/macrophage is the core component of atherosclerotic lesion. The present studies have demonstrated that monocytes have heterogeneity; this phenomenon exists conservatively between mice and human. Our and other advanced studies have demonstrated that multiple risk factors of atherosclerosis accelerate atherosclerotic lesion through promoting the Ly-6Chi monocyte differentiation. However, how Ly-6Chi monocytes participate atherosclerosis and what its potential modulation mechanism for Ly-6Chi monocyte differentiation eagerly need further explorations. Our study aim to observe how different monocyte subset transmigrate to sub-endothelial layer and differentiate into macrophage; elucidate the different the abilities of different monocyte subset contributes to inflammation response and subendothelial transmigration; further explore the modulation mechanism of monocyte subset differentiation and try to find the possible intervention approach; finally, our study evaluate the relationship between monocyte subset and vulnerability of coronary atherosclerotic plaques in patients with coronary heart diseases, therefore expand new way for the prevention and treatment of atherosclerotic cardiovascular diseases.

英文关键词： atherosclerosis；inflammatory monocytes；probucol；homocysteine；oxidative stress