炎症反应造成的生物伤在呼吸机诱导肺损伤(VILI)中发挥关键作用，对肺组织造成二次打击，影响预后。如能在转录及转录后水平抑制炎症激活可减轻VILI。lncRNA参与损伤后表观调控的研究日益深化，但在VILI炎症调控中作用尚不清楚。我们通过转录组测序发现VILI早期巨噬细胞吞噬死亡细胞后lncRNA-EPS表达下调，可能参与炎症小体激活。结合最新研究进展，我们提出假说：VILI形成后巨噬细胞清除死亡细胞时诱导lncRNA-EPS下调，对asc基因转录抑制作用削弱，导致NLRP3炎症小体激活加重损伤，外源性lncRNA-EPS有望成为治疗靶点。拟采用小鼠VILI模型，利用慢病毒转染、ChIP等手段，在分子、细胞及整体水平阐明正压通气中lncRNA-EPS作为刹车分子，在转录水平调控VILI相关炎症反应。研究结果有助于明确VILI炎症激活和组织损伤新机制，为进一步优化通气策略提供理论和实验依据。

Biotrauma caused by inflammatory response plays a key role in ventilator induced lung injury (VILI), causing secondary hit to pulmonary cells, which is closely related to a poor prognosis. It may be a novel strategy to alleviate lung injury that inhibiting excessive pro-inflammation of macrophages by transcriptional and post–transcriptional regulation. It has been well proved that long noncoding RNAs (lncRNAs) regulate gene expression in diverse biological contexts in epigenetic level. However, it is still poorly known what the role of lncRNAS in inflammation or tissue injury in mechanical ventilation. Previously, we found a number of differentially expressed lncRNAs by RNA-seq. lncRNA-EPS was significantly downregulated via macrophages phagocytosis of the dead cells. lncRNA-EPS might affect activation of NLRP3 inflamasome as well. Consequently, summing lastest reported mechanism of lncRNA-EPS, we hypothesize: expression of novel lncRNA-EPS is downregulated in infiltrated macrophages through TRL4/MD2 pathway in VILI; decreased lncRNA-EPS, which transcriptionally inhibits asc gene expression, leads to NLRP3 inflammasome activation; the changes of inflammatory status aggravate alveolar epithelial cells damage; exogenous lncRNA-EPS is expected to become a therapeutic target for VILI. In this study, we plan to prove our hypothesis in vivo using the wild type and lncRNA-EPS overexpressed mice with VILI model. Moreover, macrophages with alveolar epithelial cells will be co-cultured in vitro. Lentivirus transfection, RNA interference, RIP, ChIP and other experimental methods will be applied to reveal lncRNA-EPS-mediated inflammation in acute phage of VILI. Within this study, we anticipate to investigate the underlying mechanism of lncRNA-EPS as a key "brake molecular" in tissue impair following VILI, and explore a novel therapeutic target to improve outcome based on theoretical and experimental evidence.