上皮细胞炎症损伤在ALI/ARDS发生发展中至关重要。我们前期发现硒过氧化物酶(Prdx)6保护小鼠ALI，但Prdx6转基因鼠ALI肺部炎症并未明显减轻，且ARDS患者和ALI小鼠BALF内Prdx6升高并和疾病严重度相关；Prdx6刺激上皮细胞致细胞炎症损伤、凋亡及自噬增强并活化TLR4、NFκB，提示Prdx6在胞外可能介导上皮细胞炎症损伤而加重ALI。本项目拟采用Prdx6联合刺激构建小鼠和细胞ALI模型，通过基因编辑和小分子药物干预观察胞外Prdx6对上皮细胞炎症损伤及ALI的作用，进而确立胞外Prdx6通过TLR4-NFκB通路发挥作用的分子靶点和调控机制，并探索Prdx6细胞内外转运模式。本研究将揭示胞外Prdx6在ALI中的作用及分子机制，为ALI的治疗提供新思路。

The inflammatory injury in epithelia is of crucial importance in development and progression of acute lung injury(ALI)/ acute respiratory distress syndrome(ARDS). Our previous work showed that peroxiredoxin 6 (Prdx 6) protected mice from ALI, while ALI was not attenuated in Prdx6 transgenic mice. Prdx6 in BALF from ARDS patients or ALI mice were elevated and associated with disease severity; Stimulation with Prdx6 activated TLR4-NFκB pathway in epithelial cells and led to inflammatory injuries of enhanced cell atopsis and autophage, which indicated that extra-celluar Prdx6 might mediate epithelial inflammatory damage and aggravate ALI. This project will use LPS and CLP ALI models and cell inflammatory model stimulated with Prdx6 as combination in order to observe the effects of extracellular Prdx6 on epithelial inflammatory injury and ALI. Furthermore, by using gene editing and small molecule drug intervention, this project will test the mechanisms and major molecular targets of extracellular Prdx6 through TLR4-NFκB. This project will also explore the cell transport patterns of Prdx6 in and out pulmonary epithelia. This study will reveal the roles and molecular mechanisms of extracellular Prdx6 in ALI, in order to provide new insights into the treatment of ALI.