炎症消退调控障碍导致炎症失控是急性肺损伤发病的重要机制。脂氧素是机体最重要内源性抗炎促消退介质,为炎症反应刹车信号。在前期证实ARDS病人脂氧素浓度和受体表达明显下调基础上，结合我们新近发现脂氧素可抑制内毒素诱导的肺泡Ⅱ型上皮细胞凋亡,并可主动促进肺泡上皮屏障修复等线索。我们推测:脂氧素生成或信号转导障碍可能是急性肺损伤发病的重要机制。为此，我们拟采用雾化吸入脂多糖建立大鼠急性肺损伤模型,应用实时定量PCR、流式细胞仪、高效液相-质谱联用、激光共聚焦显微镜、western blot等技术,动态观察肺组织脂氧素及其受体变化规律；研究脂氧素对肺泡上皮细胞凋亡、增殖及对肺泡上皮屏障修复的影响并探讨具体机制；比较脂氧素与角质细胞生长因子对肺泡上皮屏障保护机制的异同性；进而在大鼠肺损伤模型，应用脂氧素受体激动剂和siRNA技术,进一步验证结果。旨在揭示急性肺损伤发病新机制并为探寻防治新靶标提供依据。

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS)consisting of acute hypoxemic respiratory failure，occur with a high incidence and mortality. The Pathological changes seen in ALI/ARDS comprise diffuse alveolar damage,alveolar capillary damage,disruption of the alveolar epithelium and devastating lung fibrosis.The degree of alveolar epithelial injury is an important predictor of the outcome such as duration of mechanical ventilation and survival.Recent studies propose that overexpress apoptosis pathway may be one of the mechanisms leading to epithelial injury and death.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. lipoxin can promote alveolar epithelial barrier repair and have anti-apoptosis effect. Based on the finding, our Hypothesis is that disorder of lipoxin is the important mechanism of acute lung injury. The main aim of this grant is to find the mechanism of lipoxin on lung epithelial proliferation、being anti-apoptosis and promoting alveolar epithelial barrier repair.lipoxin may be used as potential novel therapeutic agent for ARDS through promoting lung epithelial proliferation and being anti-apoptosis。