The optimal oxygen concentration is unclear for normothermic machine perfusion (NMP) of livers from donation after circulatory death (DCD). Our purposes were to investigate the effect of air-ventilated NMP on the DCD liver, analyze the underlying mechanism and select the targets to predict liver functional recovery with NMP. NMP was performed using the NMP system with either air ventilation or oxygen ventilation for 2 h in the rat liver following warm ischemia and cold-storage preservation. Proteomics and metabolomics were used to reveal the significant molecular networks. The bioinformation analysis was validated by administering peroxisome proliferator activator receptor-γ (PPARγ) antagonist and agonist via perfusion circuit in the air-ventilated NMP. Results showed that air-ventilated NMP conferred a better functional recovery and a less inflammatory response in the rat DCD liver; integrated proteomics and metabolomics analysis indicated that intrahepatic docosapentaenoic acid downregulation and upregulation of cytochrome P450 2E1 (CYP2E1) expression and activity were associated with DCD liver functional recovery with air-ventilated NMP; PPARγ antagonist worsened liver function under air-oxygenated NMP whereas PPARγ agonist played the opposite role. In conclusion, air-ventilated NMP confers a better liver function from DCD rats through the DAP-PPARγ-CYP2E1 axis; CYP2E1 activity provides a biomarker of liver functional recovery from DCD.

循环性死亡 (DCD) 后捐献肝脏的常温机器灌注 (NMP) 的最佳氧浓度尚不清楚。我们的目的是研究通风 NMP 对 DCD 肝脏的影响，分析其潜在机制并选择预测 NMP 肝功能恢复的目标。NMP 使用 NMP 系统在热缺血和冷藏保存后在大鼠肝脏中进行 2 小时的空气通风或氧气通风。蛋白质组学 和代谢组学用于揭示重要的分子网络。通过在通风的 NMP 中通过灌注回路施用过氧化物酶体增殖物激活受体-γ (PPARγ) 拮抗剂和激动剂来验证生物信息分析。结果表明，空气通风的 NMP 在大鼠 DCD 肝脏中赋予了更好的功能恢复和更少的炎症反应；整合蛋白质组学 和 代谢组学分析表明肝内二十二碳五烯酸下调和上调细胞色素 P450 2E1 (CYP2E1) 表达和活性与空气通气 NMP 后 DCD 肝功能恢复相关；PPARγ拮抗剂在空气氧合的NMP下使肝功能恶化，而PPARγ激动剂起相反的作用。总之，空气通风的 NMP 通过 DAP-PPARγ-CYP2E1 轴赋予 DCD 大鼠更好的肝功能；CYP2E1 活性提供了从 DCD 中恢复肝功能的生物标志物。