机械通气相关肺损伤（VILI）可增加围术期死亡率，是临床上亟待解决的重要问题，但其发病机制尚未研究清楚。前期研究发现，在VILI中c-Abl、MMP-9高表达是调控紧密连接蛋白和细胞通透性的关键基因，但其调控机制不明。通过预测和预实验验证ELK1是MMP-9的潜在上游因子，c-Abl的表达受其SUMO化修饰影响，VILI中c-Abl的SUMO化修饰与ELK1存在相互作用。由此推测：在VILI中c-Abl发生SUMO化修饰，激活ELK1转录后上调MMP-9，调控紧密连接蛋白降低和细胞通透性增加，导致肺损伤。本研究拟构建体内、体外VILI模型，采用基因定点突变、荧光素酶报告基因检测等方法，明确c-Abl的SUMO化修饰靶点，并在体内、外逐层验证c-Abl-ELK1-MMP-9轴在VILI发生中的作用，从表观遗传学角度为防治VILI提供新靶点。

Ventilation-induced lung injury (VILI) can increase perioperative mortality, which is an important problem to be solved urgently in clinic, but its pathogenesis has not been studied clearly. Our previous studies have found that high expressions of c-Abl and MMP-9 were the key to regulate tight junction protein and cell permeability in VILI, but its mechanism remains unclear. ELK1 was a potential upstream factor of MMP-9 by predicting and validating, the expression of c-Abl was influenced by its SUMOylation, and the SUMOylation of c-Abl interacted with ELK1 in VILI. We speculated that c-Abl underwent SUMOylation in VILI, which activated the transcription of ELK1 to up-regulate the expression of MMP-9, regulated the decrease of tight junction proteins and the increase of cell permeability, leading to the lung injury. In this study, we proposed to construct the VILI models in vivo and in vitro, use gene site-directed mutation, luciferase reporter gene detection and other methods to clarify the SUMOylation target of c-Abl, and verify the role of c-Abl-ELK1-MMP-9 axis in VILI in vivo and in vitro, which providing a new target for prevention and treatment of VILI from epigenetic perspective.