ARDS失控的炎症风暴的启动机制仍不清楚。气道上皮是肺脏第一道免疫屏障，多种病原体能诱导杯状细胞分泌特异性的钙激活Cl-通道（CLCA），且CLCA-/-肺炎小鼠肺泡趋化因子CXCL含量减少，导致中性粒细胞浸润显著降低。本课题组也发现，肺内型ARDS患者肺泡CLCA含量明显升高，并随着病情缓解而降低。因此提出“病原体诱导分泌的CLCA能促进上皮细胞产生CXCL，从而启动和加重ARDS炎症发生”的假设。基于此，本项目拟：①建立肺内型ARDS小鼠模型，研究CLCA表达水平与ARDS特征的时程关系；②正向和反向干预ARDS小鼠气道CLCA表达与功能，观察对肺内CXCL含量及疾病特征的影响；③提纯CLCA并干预培养气道上皮细胞，探讨CXCL合成及信号转导通路；④探讨ARDS患者痰液及肺泡液CLCA含量，做为疾病生物预测因子的临床价值。旨在阐明上皮细胞及CLCA在ARDS发病中的始动地位及防治靶点。

The mechanism of the origination of pulmonary inflammation in ARDS is still unclear. Because airway epithelium is the first barrier of pulmonary immune system, the goblet cells` can secret a sort of specific calcium activated chloride channel (CLCA) when being induced by various kinds of pathogens. It is was reported that the chemokine CXCL in the alveolar of pneumonia model with CLCA-/- mouse decreased, in the meantime the number of neutrophils infiltration also dropped significantly. We also found that the content of CLCA in bronchoalveolar fluid (BALF) of intrapulmonary ARDS patients increased and would gradually decrease with the remission. Therefore, we puts forward a hypothesis that pathogen-induced CLCA can promote airway epithelial cells to produce CXCL, which can initiate and deteriorate the inflammation of ARDS patients. Based on this, this project aims to finish the researches as following. Firstly, a mouse model with intrapulmonary ARDS will be established, where the time relationship between the level of CLCA and the characteristics of ARDS will be studied. Secondly, the effects of positive and passive intervention in the expression and function of CLCA will be checked on CXCL content and disease characteristics. Thirdly, the CXCL synthesis and the signal transduction pathways will be investigated with the purifying CLCA interfering the airway epithelial cells of primary culture. Finally, whether the CLCA content of sputum and BALF in ARDS patients can act as biological predictor will be explored. The subject aims to clarify the role of airway epithelial cells and CLCA in the initiative and development of ARDS, in order to provide a new target of prevention and treatment for ARDS.