中性粒细胞过度活化导致失控性炎症反应是脓毒症致急性肺损伤的主要病理特征。我们的前期结果表明Protectin DX（ PDX）作为新发现的炎症消退介质能提高脓毒症小鼠生存率，并改善肺组织病理损伤。我们的预实验和其他研究提示PDX可通过MAPKs信号通路抑制NADPH氧化酶的p47phox亚基ser345位点磷酸化，进而抑制中性粒细胞活化，但仍需要充分论证。因此，我们提出研究假设：PDX可通过调节MAPKs／ser345-p47phox信号通路抑制中性粒细胞活化保护脓毒症致急性肺损伤。本项目拟采用小鼠盲肠结扎穿孔建立脓毒症致急性肺损伤模型并结合多种技术手段，首先研究PDX对小鼠急性肺损伤的影响；然后观察PDX调节中性粒细胞活化对急性肺损伤的影响；最后明确PDX调节中性粒细胞活化是否通过MAPKs/ser345-p47phox信号通路介导。本项目将为治疗脓毒症致急性肺损伤提供新的理论依据。

Uncontrolled inflammatory response caused by neutrophil hyperactivation are the main pathological features of acute lung injury induced by sepsis. Our previous study had shown that Protectin DX(PDX), a newly identified lipid mediator, increased survival in a mouse model of sepsis and protected lung injury from sepsis. And our preliminary experiment and other’s repor suggested that PDX could limit inflammatory response through depressing neutrophil hyperactivation mediated by the inhibition of Ser345-p47phox phosphorylation of NADPH-oxidase and the upstream MAPKs signal pathway. However, it still needs to be elucidated. According to these findings we hypothesize that PDX could protect acute lung injury in sepsis through inhibiting neutrophil activation by targeting the MAPKinase/Ser345-p47phox-axis. So, we will test this hypothesis in present proposal by performing cecal ligation and puncture(CLP) in mice to establish model of sepsis-induced acute lung injury, applying diverse of experimental techniques. Firstly, we will observe the effects of PDX on acute lung injury induced by sepsis. Secondly, we are going to investigate the influence of Protectin DX in regulating neutrophil activation in sepsis-induced acute lung injury. Finally, to verify whether PDX regulates neutrophil activation is mediated by the MAPKs/ser345-p47phox signaling pathway.The finding of present proposal will provide a novel therapeutic strategy in treating acute lung injury induced by sepsis.