机械通气（MV）是临床常用且不可或缺的生命支持技术，但它会以机械伤和生物伤的形式引起呼吸机诱导的肺损伤（VILI）。目前临床上除采用“保护性通气策略”外，缺乏药物干预手段。研究表明，“保护性通气策略”不能有效防范炎症介质介导的生物伤，但具体发病机制不清。所以，阐明炎症介质在VILI中的作用机制，提供相应的药物作用靶点，对临床防范VILI具有重要的现实意义。项目组前期研究发现，白三烯B4（LTB4）介导的生物伤在VILI中发挥重要作用。结合前期基因芯片和体外实验研究结果及文献报道，我们推测“LTB4的作用机制与PLCE1及其下游信号通路有关”。为此，本研究拟从肺微血管内皮细胞（PMVEC）通透性增加这一VILI的早期关键病理变化环节入手，运用基因敲除，细胞转染等分子生物学技术，通过体、内外实验研究，阐明LTB4在MV致PMVEC通透性增加中的作用机制，为药物防治VILI提供一个新的干预途径。

Mechanical ventilation (MV)，as a widely used and indispensable supportive intervention in clinical practice，can provoke ventilator-induced lung injury(VILI）by mechanical injuriy and biological injury. At present, apart from the protective ventilation strategy, no other pharmacological intervention is available to attenuate ventilator-induced lung injury.Studies have found that protective ventilation strategy can not effectively prevent biological injuriy induced by inflammatory mediators. However, the exact pathogenesis of inflammatory mediators in VILI is unclear.Therefore, it is very vaulable to provide pharmacological intervention for clinical prevention and treatment of VILI by elucidating the pathogenesis of inflammatory mediators in VILI. Our previous study found that the biological injuries induced by leukotriene B4（LTB4） play an important role in VILI (Mechanical ventilation with protective ventilation strategy can still cause excessive inflammatory response by overproduction of leukotriene B4,and then leading to lung injury in the absence of pre-existing lung injury in healthy rat.). Combined our gene chip and in vitro experimental results with related literature reports, we hypothesize that LTB4 can cause VILI through the regulation of phospholipase C epsilon-1（PLCE1）and its downstream signaling pathways. In this study, we will proceed from the early critical pathology of VILI (increased pulmonary microvascular endothelial cell permeability ) to elucidate the pathogenesis of LTB4 in increased pulmonary microvascular endothelial cell permeability induced by mechanical ventilation in vivo and in vitro by using molecular biology techniques such as gene knockout and cell transfection，so that we can provide a new therapeutic target for pharmacological intervention of ventilator-induced lung injury.