机械通气是一把双刃剑，不仅引起机械通气肺损伤，还可以诱发脑损伤。但机械通气所致“肺-脑交互”损伤发生机制迄今远未阐明。γ-氨基丁酸(GABA)作为中枢神经系统中最重要的抑制性神经递质，近年发现其不但参与脑损伤及认知功能障碍的发生，而且成为加剧肺脏损伤的重要介质，并与参与肺损伤 NF-κB、p38MAPK等炎性通路激活密切相关。尤其近期我们发现机械通气所致肺损伤模型大鼠肺、脑组织中GABA表达均明显增高。结合前期研究结果，我们推测GABA系统激活可能是机械通气所致“肺-脑交互”损伤的关键信号分子。本项目拟采用病理学、分子生物学、RNA基因干扰等技术，重点研究 GABA 系统激活对肺-脑损伤程度以及下游NF-κB、p38MAPK和STAT3信号通路的影响，探究激活的GABAR亚型，阐明GABA通路在机械通气所致肺-脑损伤的分子效应和调控机制。为临床机械通气肺、脑损伤的防治提供新思路。

Mechanical ventilation (MV) is essential for patients with acute respiratory failure.However,ventilator induced not only lung injury but also brain dysfunction. The mechanism of mechanical ventilation-induced lung-brain crosstalk injury has not been identified. Gamma-aminobutyric acid (GABA) is the most important inhibitory neurotransmitter in central nervous system. Recent studies have found that GABA is related to not only cognition impairment and brain dysfunction but also NF-κB、p38MAPK signaling pathway involved in lung injury. Our preliminary experiment showed that GABA expression of lung and brain was up-regulated in the model of ventilator induced lung injury in rat. Based on our preliminary experiment, we propose hypothesis that GABA is the key signaling pathway of mechanical ventilation-induced lung-brain crosstalk injury. Our project intends to use pathology, molecular biology, RNA gene interference detection technology to discuss the effect of GABA signaling pathways in mechanical ventilation-induced lung-brain crosstalk njury and on activation of NF-κB、p38MAPK STAT3 signaling pathway.Fuethermore, we explore the molecular mechanism of GABA signaling pathways, with a view to provide new ideas for clinical prevention of lung-brain crosstalk injury.