在急性呼吸窘迫综合征（ARDS）/急性肺损伤（ALI）的发生过程中，中性粒细胞起核心作用。凝血纤溶系统对中性粒细胞募集和活化具有重要的调控作用，但机制未明。纤溶酶原激活物抑制物-1（PAI-1）与肺损伤的预后密切相关。在肺损伤早期，PAI-1促进中性粒细胞肺内募集活化，发挥抗感染作用，但晚期中性粒细胞的过度募集活化会加重肺损伤。通过调控PAI-1使中性粒细胞发挥最大抗感染作用，同时又不造成过度肺损伤有重要的治疗意义。PAI-1/PECAM/p38MAPK/PI3K 通路与中性粒细胞的募集活化相关，本研究拟利用PAI-1敲除小鼠建立LPS-肺损伤模型，研究调控该通路对小鼠肺损伤和中性粒细胞肺内募集活化的影响，初步阐明PAI-1在肺损伤中调控中性粒细胞肺内募集和活化的机制，并探索PAI-1抑制剂在肺损伤中的治疗作用以及合适的治疗时间，最终为以PAI-1为靶点的肺损伤治疗提供依据。

Neutrophils, which were regulated by fibrinolysis and coagulation system, played a fundamental role in the pathogenesis of acute respiratory distress syndrome (ARDS)/acute lung injury (ALI). However, the mechanism of recruitment and activation of neutrophils by fibrinolysis and coagulation system was not elucidated. The plasminogen activator inhibitor-1 (PAI-1), an important member of fibrinolysis and coagulation system, was positively correlated with mortality in patients with ARDS/ALI. In early phase of ARDS/ALI, PAI-1 promoted the recruitment and activation of neutrophils in alveolar, thus increasing the anti-infectious effect, but excessive aggregation of neutrophils could exacerbate the injury of alveolar in the following period. It is of great importance to take the advantage of PAI-1 to maximize the anti-infectious effect of neutrophils, and at the same time, minimize the damage in ALI. PAI-1/PECAM/p38MAPK/PI3K pathway is closely related with the recruitment and activation of neutrophils. In order to clarify the mechanism of interations between this pathway and neutrophils in alveolar, find out the appropriate therapeutic protocol of PAI-039, an inhibitor of PAI-1, and provide theoretical basis of the therapy aimed at PAI-1, we would carried out this study by LPS-ALI model in PAI-1 knockout mice.