肺微血内皮细胞（PMVEC）通透性增加是ARDS发生的关键环节，其发生机制与PMVEC骨架蛋白及相关的信号转导变化密切相关。本课题检测大鼠PMVEC中埃兹蛋白、根蛋白、膜突蛋白（Ezrin, radixin, moesin, ERM）的表达、分布及其与肌动蛋白的关系。观察脂多糖（LPS）、肿瘤坏死因子（TNF-α）等诱导大鼠PMVEC单层通透性增加过程中ERM 3种蛋白的变化。构建ERM 3种蛋白基因RNA干扰慢病毒，观察抑制ERM基因表达后对PMVEC通透性的影响。检测质粒转染高表达ERM蛋白后上述过程的变化。研究Rho相关激酶、PKC、MAPK等对ERM 蛋白的调节作用。分别探讨抑制或高表达ERM 蛋白后对上述蛋白激酶的反馈调节机制，针对ERM蛋白作用环节，采取干预措施影响PMVEC内信号转导，以期减轻炎性介质诱导的PMVEC单层通透性增加。

The key of pathogenesis on acute respiratory distress syndrome(ARDS) is the increase of pulmonary microvascular endothelial cells(PMVEC) permeability,which is related to the cytoskeletal protein and its signal transduction. The aim of this study is firstly to examine the expression, distribution of ezrin, radixin, moesin (ERM) on rat PMVEC, then, investigate the relation of ERM and F-actin in cells. Secondly, the changes of ERM are assessed on the regulation of endothelial hyperpermeability after exposure of PMVEC to lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α). The technology of RNA interference through lentiviral vector inhibiting ERM expression and plasmid transfection overexpressing ERM is used to investigate the regulation of those proteins in endothelial permeability, respectively. We also explore influence of protein kinases (Rho-associated kinase, protein kinase C and mitogen activated protein kinases) on ERM. The feedback regulation mechanism of ERM on protein kinases is investigated by RNA interference and plasmid transfection overexpression, respectively. To alleviate the injury of PMVEC induced by inflammation, we intend to intervene in the signal transduction of PMVEC according to different regulatory mechanism of ERM.