炎症消退调控障碍导致炎症失控是急性呼吸窘迫综合征发病的重要机制。脂氧素是机体最重要内源性抗炎促消退介质,为炎症反应的“刹车信号”。在前期证实脂氧素促进肺泡液体清除率，保护肺损伤作用的基础上，结合我们新近发现脂氧素可促进巨噬细胞吞噬凋亡的中性粒细胞以及脂氧素促进M2型肺泡巨噬细胞增多，抑制M1型肺泡巨噬细胞表达等线索。我们推测：脂氧素调控巨噬细胞表型转换可能是促进炎症消退的重要机制。为此，我们拟采用静脉注入内毒素型大鼠ARDS炎症损伤模型, 培养人原代单核细胞，巨噬细胞，应用实时定量PCR、流式细胞仪、激光共聚焦显微镜、western blot等技术,动态观察脂氧素及其受体，巨噬细胞表型变化规律；探讨脂氧素对巨噬细胞M1型和M2型的影响及相互间转化的机制；进一步应用脂氧素受体激动剂, 抑制剂和siRNA技术验证我们假说。旨在揭示促炎症消退新机制并为防治ARDS提供实验资料。

Acute respiratory distress syndrome (ARDS) consisting of acute hypoxemic respiratory failure, occur with a high incidence and mortality. Lipoxins (LXs) are unique structures derived from arachidonic acid. Lipoxins were the first mediators recognized to have dual anti-inflammatory and pro-resolution activities, which have been described as the endogenous “braking signal” for inflammation. We previous research shows that the lipoxin concentration and lipoxin receptor expression decrease in ARDS patients. We also find lipoxin not only promotes neutrophils apoptosis and efferocytosis, but also increases M1 transfer into M2 macrophages. Base on these findings, our hypothesis is that lipoxin may mediate M1 and M2 transformation to promote inflammation resolution, which is the important mechanism of acute lung injury. Therefore, low dose LPS induced lung injury was established, primary monocytes and macrophages were also isolated and cultured, blood and BALF from ARDS patients were harvest. Real-time PCR, flow cytometry, laser confocal microscope and western blot et al were used to measure the dynamic of lipoxin, lipoxin receptor and macrophage phenotype changes, discuss the effect of lipoxin on M1 and M2 phenotype. Finally, to gain a better understanding of the mechanisms, we also investigated the effect of BML-111 (ALX agonist), butoxycarbonyl-Phe-Leu-Phe-Leu-Ph (BOC-2 [ALX antagonist]) and siRNA on macrophages phenotype in ARDS. The main aim of this grant is to reveal a novel mechanism of pro-resolution and provide experimental data explore the prevention and treatment of ARDS.