肺泡水肿液清除（AFC）是降低ALI/ARDS病死率的有效途径。上皮钠通道（ENaC）是AFC的关键环节。申请人在前期博士课题研究中发现PI3K/Akt通路是参与AFC的重要信号链，但其下游的信号链接仍未完全阐明。作为PI3K/Akt信号链下游必经的连接“桥梁”，WNK4-SPAK通路是维持钠水转运的一条中心通路，是AFC强有力的调节器，具有理想可干预性，但与ENaC的关系目前尚不明确。本项目以原代肺泡上皮细胞和ALI动物模型为研究对象，以WNK4-SPAK通路是否调控ENaC为研究核心，采用基因过表达、RNAi干扰等方法，从体内和体外两个层面研究WNK4-SPAK通路调节ENaC表达和活性的功能，探讨其在AFC中的作用，最终揭示WNK4-SPAK通路与AFC的分子链接基础。研究结果将进一步完善PI3K/Akt信号链在AFC中扮演的角色,并为ALI/ARDS防治提供有效的干预靶点。

Alveolar fluid clearance (AFC) is an effective way to reduce the mortality rate of ALI/ARDS.The epithelial sodium channel (ENaC) is a critical procedure in AFC. In the previously doctoral research project, PI3K/Akt pathway was an important signaling chain in AFC, but its downstream signaling interlinkage has not been completely clarified.As an inevitable connection"bridge" in the downstream of PI3K/Akt signaling chain, WNK4-SPAK pathway was a central way which maintained sodium and water transport and was a powerful regulator in AFC with ideal intervention,but the relationship with ENaC has not been clear so far .The primary alveolar epithelial cell and ALI animal model are served as subjects, whether the regulation of ENaC is by WNK4-SPAK pathway as a corn and the methods including gene overexpression and RNAi interference are used to investigate the function of WNK4-SPAK pathway in the regulation of ENaC expression and activity in vivo and in vitro, which explore the effect of the pathway in AFC and ultimately reveal the molecular interlinkage foundation between WNK4-SPAK pathway and AFC.The results of the study might further improve the role of PI3K/Akt signaling chain played in AFC and provide an effective intervention target for the prevention and treatment of ALI/ARDS.