肺泡水肿液清除（AFC）是治疗ALI/ARDS的重要步骤。而上皮钠通道（ENaC）是AFC的关键环节，一定程度上决定了ALI/ARDS的预后。新近发现mTORC2的重要组成部分Rictor和mSIN1能与SGK-1的疏水序基（HM）位点结合后活化该酶。我们在前期NSFC项目（30971303）的研究中发现：激活SGK-1能上调ENaC亚基表达，显著促进ALI/ARDS肺泡水肿液的清除。结合前期的工作基础，我们推测mTORC2可能是调控ENaC及AFC重要的上游信号通路。本课题拟通过基因转染，RNA干扰,基因敲除,膜片钳技术等手段，采用原代肺泡上皮细胞、C57B/L6小鼠及基因敲除小鼠的ALI模型，探讨mTORC2/SGK-1信号通路对ENaC作用的分子机制，是对我们前期研究的进一步深入和完善，对完整阐明调控ENaC上游的信号通路具有实际意义，为临床治疗ALI/ARDS提供新线索和分子基础

Alveolar fluid clearance (AFC) is an important step in the treatment of ALI / ARDS.The epithelial sodium channel (ENaC) is a key procedure in AFC, which determines the prognosis of ALI / ARDS to some extent.Recently rictor and mSIN1,two important components of mTORC2,are found to activate SGK-1 by binding the site termed the hydrophobic motif (HM).In our previous NSFC project (NO:30971303),we discovered that activation of SGK-1 could up-regulate the expressions of ENaC subunits to significantly promote AFC in ALI / ARDS.We speculate that mTORC2 may be an important upstream signaling pathway in regulation of ENaC and AFC on the basis of our previous investigation.Primary alveolar epithelial cells and ALI model of C57B/L6 mice and gene knockout mice are intended to be adopted by the methods including gene transfection, RNA interference and gene knockout to investigate the molecular mechanisms of mTORC2/SGK-1 signaling pathway in regulation of ENaC,which is the further improvement on our previous study,show the practical significance of clarifying the complete upstream signaling pathways in regulation of ENaC and provide a new clue and molecular basis for the clinical treatment of ALI / ARDS in this project.