巨噬细胞上的Tim-3在阿司匹林诱导的动脉粥样硬化稳定斑块中的作用

项目名称： 巨噬细胞上的Tim-3在阿司匹林诱导的动脉粥样硬化稳定斑块中的作用

项目编号： No.81500339

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： 阎文江

作者单位： 山东大学

项目金额： 18万元

中文摘要： 巨噬细胞引起的炎症是动脉粥样硬化（AS）斑块易损的关键。不同分型的巨噬细胞对AS斑块影响存在区别：M1型处于炎性状态，易于坏死凋亡，斑块稳定性下降；M2型抑制M1细胞的坏死、吞噬凋亡的M1型细胞，缓解AS炎症，稳定斑块。Tim-3是巨噬细胞M2极化的关键分子并且预实验表明阿司匹林体内外均可以促进Tim-3的表达。据此本课题拟运用多种实验方法，体内外研究相结合，探讨aspirin诱导Tim-3升高的分子机制，验证Tim-3是aspirin通过巨噬细胞诱导斑块稳定的关键分子，明确aspirin及Tim-3双重干预对AS斑块稳定性的作用。本课题通过研究Tim-3在aspirin诱导的稳定斑块中的作用，阐明aspirin可以通过巨噬细胞上的Tim-3对AS斑块起作用。本研究将为AS治疗提供协同双干预靶点。

中文关键词： T细胞免疫球蛋白粘蛋白样分子3；巨噬细胞极化；阿司匹林；斑块稳定性；动脉粥样硬化

英文摘要： The inflammation response caused by macrophages is the key point in atherosclerosis vulnerable plaque. Different types of macrophages have different function in AS plaque: M1 which is apt to apoptosis contributes to decreasing the plaque stability; M2 which can inhibit the apoptosis of M1 and phagocytose apoptotic M1 macrophages, contributing to the resolution of inflammation, increase the plaque stability. Tim-3 is the key molecule in macrophages M2 polarization and we have found that aspirin could upregulate the expression of Tim-3 both in vivo and in vitro. Comprehensive experimental methods are involved in this issue (1) to investigate the mechanism of how aspirin increase Tim-3 expression; (2) to verify the role of Tim-3 on macrophages in aspirin induced stable plaque; (3) to confirm the co-function of Tim-3 and aspirin in AS plaque stability. We can illuminate the role of Tim-3 on macrophages in atherosclerosis stable plaque induced by aspirin and provide synergistic-intervening targets for AS treatment.

英文关键词： Tim-3;Macrophages polarization;Aspirin;Plaque stability;Atherosclerosis