呼吸道菌群失调致AMPK内源性激动剂GA下调对单肺通气后肺断气复气损伤的作用和机制

单肺通气是胸外科常用技术，术侧肺术中塌陷、术毕复张通气，该断气复气过程可致肺损伤如炎症、水肿等，甚至急性呼吸窘迫综合征。呼吸道定植菌已被发现在多种肺疾病包括肺损伤中发挥重要作用。但其是否参与肺断气复气损伤及机制仍不清楚。我们前期通过构建动物模型并进行16S rDNA测序发现断气复气及抗肾素-血管紧张素系统（RAS）干预均可影响呼吸道定植菌，代谢组学分析提示呼吸道定植菌与内源性AMPK激动剂山羊豆碱（GA）水平相关。根据联合组学分析及文献检索，我们假设呼吸道定植菌可被肺断气复气过程及RAS影响，并可通过GA对肺断气复气损伤发挥作用。本研究拟通过在体水平行干预菌群等措施后构建SLV肺断气复气损伤模型明确呼吸道定植菌在该过程中如何被调控，并在体内外水平通过多组学分析及基因编辑等技术明确其是否通过代谢物GA影响下游AMPK激活发挥作用。本项目的完成可望为胸外科术后肺损伤防治提供新的思路和靶点。

Single lung ventilation (SLV) has been widely used during thoracic surgery, which helps make the lung on the surgical side collapse and re-expanse after surgery. The process of collapse-re-expansion could induce lung injury and even severe complications such as acute respiratory distress syndrome (ARDS). Pulmonary host microflora was found critical during both acute and chronic pulmonary diseases development. But whether it’s involved in this kind of lung injury induced by collapse-re-expansion remains unknown. According to our previous study results, with the animal modeling SLV, 16S rDNA sequencing revealed that the process of collapse and re-expanse after SLV and the intervention of anti-renin angiotensin system (RAS) therapy might influence the pulmonary host microflora on the injured side, which might be potentially associated with the level of metabolite galegine (GA), a kind of AMPK agonist, based on the analysis combining metabolomics test and 16S rDNA sequencing. Thus, we came up with the hypothesis that pulmonary host microflora can be influenced by the process of collapse-re-expansion and RAS, which participates in the lung collapse-re-expansion injury via regulating GA and the activation level of AMPK. This study aims to investigate how the pulmonary host microflora is influenced in the lung collapse-re-expansion injury in vivo, and its potential role in this process via regulating GA and the activation of AMPK through multiomics analysis and gene editing technique both in vivo and in vitro. We hope this study could shed new insights into understanding the role of pulmonary microflora in acute lung injury after SLV and help explore novel therapeutic targets for patients after SLV in the future.