肺微血管内皮屏障功能损伤及通透性增加是急性呼吸窘迫综合征（ARDS）的特征,内皮细胞屏障功能受细胞间连接及骨架蛋白的动态调节。本课题分离和培养大鼠肺微血管内皮细胞（PMVEC），鉴定PMVEC膜异亮氨酸－谷氨酸Ras和GTP酶激活蛋白（IQGAP)亚型、观察炎症诱导PMVEC屏障功能损伤过程中IQGAP亚型的变化及其与肺微血管内皮屏障功能损伤的关系。构建IQGAP基因RNA干扰慢病毒，观察抑制IQGAP基因表达后对肺微血管屏障功能的影响，检测质粒转染高表达IQGAP后上述过程的变化。探讨FAK、RhoA、Cdc42及Rac1对IQGAP的反馈调节机制。针对上述IQGAP亚型的变化及其作用环节，采取干预措施改变细胞内信号转导，通过调控PMVEC肌动蛋白骨架，以期减轻炎症诱导的PMVEC屏障功能损伤。初步明确IQGAP在肺微血管内皮屏障功能的调控作用环节及信号转导机制。

Hallmark of acute respiratory distress syndrome (ARDS) is pulmonary microvascular endothelial barrier injury and its increase of permeability. Barrier function of pulmonary microvascular endothelial cells(PMVEC) is dynamically regulated by intercellular junctions and cytoskeletal proteins. Subtype of IQRas GTPase-activating protein (IQGAP) are identified in cultured PMVECs from rat. The aim of this study is firstly to examine the expression of IQGAPs on PMVECs and investigate the relation between change of subtype of IQGAP and pulmonary microvascular endothelial barrier disruption in inflammation. The technology of RNA interference through lentiviral vector inhibiting IQGAP expression and plasmid transfection overexpressing IQGAP is used to explore the regulation of those proteins in barrier function disruption of PMVEC induced by inflammation, respectively. The feedback regulation mechanism of FAK，RhoA，Cdc42 and Rac1 on IQGAP are explored. To ameliorate the barrier function injury of PMVEC induced by inflammation, we also intend to intervene in the signal transduction pathway and actin remodeling of PMVEC according to different the sites of action of IQGAPs. These results may further elucidate the sites of action and its signal transduction mechanism of IQGAPs on barrier function of pulmonary microvascular endothelium .