失控性炎症反应是引起 ALI/ARDS的中心环节。我们前期证实IL-33在ARDS中表达异常升高，发挥炎症促进作用。进一步发现AT-II细胞是IL-33作用靶点；IL-33能激活AT-II细胞内多条信号通路，诱导致炎因子释放。在此基础上，提出“ALI/ARDS中IL-33异常表达升高，其通过JAK/STAT3、PI3K/Akt、p38/MAPK等信号通路活化AT-II细胞，促进失控性炎症，推动ALI/ARDS进程”的假说。拟于人AT-Ⅱ细胞损伤模型和小鼠肺损伤模型中，使用IL-33R(－/－)基因敲除小鼠、腺病毒载体、基因芯片杂交、小分子抑制剂，结合免疫荧光、流式细胞术、WB、ELISA、Realtime-PCR等技术；从分子水平、细胞和动物模型揭示IL-33活化AT-Ⅱ细胞在ALI/ARDS失控性炎症中的作用和分子机制，为阐明ALI/ARDS发病机制提供基础研究证据，开拓其防治新思路。

Uncontrolled pulmonary inflammation lies at the center of the pathology of acute lung injury (ALI) /acute respiratory distress syndrome(ARDS). In our previous study we found that over-expression of IL-33 leads to progression of inflammation in ARDS. We further found that alveolar epithelial typeⅡcell (AT-II) might be the target cell of IL-33. IL-33 can activate different signal transduction pathways in AT-II, and result the release of pro-inflammatory cytokines. On this basis, we put forward the hypothesis: abnormal high expression of IL-33 activate JAK/STAT3、PI3K/Akt、and p38/MAPK signaing pathways in AT-II. It then promote uncontrolled pulmonary inflammation of ALI/ARDS. In this study, we will utilize an in vitro AT-II cell injury model and in vivo lung injury in mice. IL-33(-/-) mice、adenovirus vector、gene chip hybridization、molecule inhibitors、immunofluorescence、flow cytometry、WB、ELISA and Realtime-PCR technologies will be used. We will certificate the effects of IL-33 in AT-II cells and its underlying molecular mechanism of uncontrolled pulmonary inflammation of ALI/ARDS. This may offer a novel therapeutic strategy for ARDS/ALI.