TREM-1在慢性间歇性低氧诱导的动脉粥样硬化过程中对巨噬细胞极化的调控及机制研究

阻塞型睡眠呼吸暂停综合征（OSAS）是一种常见的睡眠期疾病，夜间反复发生的慢性间歇性低氧（CIH）是其主要的病理生理机制。OSAS是动脉粥样硬化（AS）的独立危险因素，巨噬细胞在AS的形成中扮演核心角色，促炎症性M1型巨噬细胞极化的作用尤为重要。髓样细胞触发受体-1（TREM-1）激活在巨噬细胞参与AS形成中起决定作用，前期我们研究发现，TREM-1激活可促进巨噬细胞活化、增加促炎因子分泌和增强巨噬细胞吞噬能力，扩大炎症反应，但具体机制不清楚。因此，我们提出假说，CIH激活巨噬细胞表面TREM-1，参与调节M1型巨噬细胞极化过程，启动了NF-κB-HIF-1β信号通路，进而导致AS。本研究拟应用CIH诱导AS的小鼠模型和小鼠巨噬细胞株，探讨CIH诱导巨噬细胞向M1型巨噬细胞分化过程中TREM-1的动态表达变化规律及相关信号通路，为更好地阐明OSAS所致AS的分子机制及探索相关干预奠定基础。

Obstructive sleep apnea syndrome (OSAS) is a common sleep disorder with higher prevalence, which is characterized by chronic intermittent hypoxia (CIH). It has been shown that OSAS is an independent risk factor for atherosclerosis. Macrophage plays a critical role during the process of atherosclerosis, among which, the differentiation of monocytes to pro-inflammatory M1-like macrophage is essential. Triggering Receptor Expressed on Myeloid Cells-1(TREM-1) can regulate the M1 macrophage polarization. Meanwhile, our previous data have shown that TREM-1 can promote macrophages activation, increase pro-inflammatory factor secretion and enhance macrophage phagocytosis. However, the molecular mechanism remains unclear. Thus, our hypothesis is that it is a regulation of macrophage M1 polarization by TREM-1 through triggering NF-κB-HIF-1β signal pathway during chronic intermittent hypoxic induced atherosclerosis. In this study, we plan to explore the relationship between dynamic trends of TREM-1 and macrophage M1 polarization, further the signal pathways, by using mouse model of atherosclerosis and murine macrophage strain. Our research will clarify the mechanism of OSAS induced atherosclerosis in a new sight, and provide the theoretical basis for the development of new therapy strategy about atherosclerosis.