炎症消退障碍所致的失控性炎症为ARDS重要发病机制。消退素D1是新近发现的重要内源性抗炎促消退介质。在我们发现LPS诱导COX-2双峰表达，消退素D1促进COX-2第二峰及其产物PGD2表达，NF-κB p50/p50介导COX-2促消退作用基础上。我们推测：消退素D1作用于NF-κB/COX-2/PGD2轴促进炎症消退。为此，拟采用原代肺成纤维细胞、内毒素性小鼠ARDS模型，应用EMSA-supershift、激光共聚焦、双荧光素酶报告基因、生物信息学、ChIP、DNA pull down等技术，观察炎症发生期和消退期COX-2、PGD2和PGE2合成酶及衍生物的差异性；探讨NF-κB p50/p50介导COX-2第二峰表达的具体机制；研究消退素D1调控NF-κB/COX-2/PGD2轴的具体通路；并应用基因过表达、敲低和基因敲除技术验证假说；为防治ARDS新策略提供实验依据。

The uncontrolled inflammation caused by disregulated resolution of inflammation is the most important mechanism in the development of ARDS. Resolvin D1(RvD1) is one of the important endogenous anti-inflammatory and pro-resolution mediators. Our previous study demonstrated that lipopolysaccharide (LPS) induces COX-2 bimodal expression, RvD1 promotes the expression of the second peak of COX-2 and its production prostaglandin D2 (PGD2). Moreover, the new function of COX-2 in promoting inflammation resolution is mediated by NF-κB p50/p50. Therefore, we hypothesize that RvD1 could act on the NF-κB/COX-2/PGD2 axis to promote the resolution of inflammation. We will use EMSA-supershift, laser confocal, dual-luciferase report gene, bioinformatics, ChIP, DNA pull down to measure the different expression of COX-2, PGD2 and PGE2 synthetase and related derivatives. To discuss the specific mechanism of NF-κB p50/p50 mediated the expression of COX-2. And to confirm the underlying mechanism of RvD1 regulating NF-κB/COX-2/PGD2 pathway. In addition, the methods for overexpression of related gene, siRNA interference and knockout technology will be used to verify the hypothesis. The main aim of this grant is to reveal a novel mechanism of the resolution of inflammation and provide experimental data for the prevention and treatment of ARDS.