炎症反应激活诱发易损斑块破裂，不仅是动脉粥样硬化病变进展的重要诱因，也是引起急性冠脉事件的主要原因。从抗炎角度寻找干预靶点被认为是最有希望的药物治疗方向。我们的前期研究表明，核受体RXRa在动脉粥样硬化斑块局部表达显著上调，在炎症激活状态的巨噬细胞，RXRa发生核移位，可能通过非基因型方式直接作用于炎症信号通路。据此我们提出如下假说：巨噬细胞等炎症细胞中的RXRa通过移位到胞浆，与胞浆炎症信号通路的某些蛋白直接相互作用，激活炎症；阻断RXRa核移位或拮抗其作用，可能抑制炎症并稳定斑块。本项目拟在前期工作的基础上，以核受体RXRa非基因型作用与动脉粥样硬化炎症的关系为主线，阐明RXRa在巨噬细胞亚细胞定位改变及调控炎症信号通路的分子机制，探讨RXRa作为调控斑块稳定性药物分子靶点的可能性，以期发现新的动脉粥样硬化炎症反应机制和干预靶点，为寻找和开发改善斑块稳定性的药物提供新思路和新手段。

Inflammation plays an pivocal role in atherosclerotic plaque rupture, which is the most important inducer of atheroclerosis development as well as the main cause of acute coronary syndrome. It has been considered that anti-inflammation would be the most promising target for drug therapy. According to previous experiments, we found there was an significant high expression of nucler receptor RXRa in atherosclerotic plaque. RXRa translocated from nucleus to cytoplasm in activated macrophages under inflammatory conditions, which indicated an non-genomic effect between RXRa and inflammatory pathway. Our hypothesis is that, RXRa activate inflammation by translocating from nucleus to cytoplasm and interacting with some certain protein in inflammatory pathway directly. Atherosclerotic inflammaiton could be inhibited by blocking RXRa translocation or its intraction with other proteins, which also contribute to improved plaque stability. On basis of previous works, we plan to investigate the relationship between RXRa non-genomic effect and atherosclerotic inflammation, clarify the mechanism of RXRa translocation and regulation of inflammatory pathway, and explore the possiblity of RXRa as an new molecular target of improving plaque stability. We expect to find new mechanism, new target and new train of thought in atheroclerotic inflammation and drug target for improving plaque stability.