Second Affiliated Hospital, Dalian Medical University, Dalian 116044, People's Republic of China; School of Pharmaceutical Sciences, Medical School, Shenzhen University, Shenzhen 518061, People's Republic of China.
Second Affiliated Hospital, Dalian Medical University, Dalian 116044, People's Republic of China; College of Pharmacy, Dalian Medical University, Dalian 116044, People's Republic of China.
J Hazard Mater. 2023 Sep 15;458:131890. doi: 10.1016/j.jhazmat.2023.131890. Epub 2023 Jun 19.
Air pollution represented by particulate matter 2.5 (PM2.5) is closely related to diseases of the respiratory system. Although the understanding of its mechanism is limited, pulmonary inflammation is closely correlated with PM2.5-mediated lung injury. Soluble epoxide hydrolase (sEH) and epoxy fatty acids play a vital role in the inflammation. Herein, we attempted to use the metabolomics of oxidized lipids for analyzing the relationship of oxylipins with lung injury in a PM2.5-mediated mouse model, and found that the cytochrome P450 oxidases/sEH mediated metabolic pathway was involved in lung injury. Furthermore, the sEH overexpression was revealed in lung injury mice. Interestingly, sEH genetic deletion or the selective sEH inhibitor TPPU increased levels of epoxyeicosatrienoic acids (EETs) in lung injury mice, and inactivated pulmonary macrophages based on the MAPK/NF-κB pathway, resulting in protection against PM2.5-mediated lung injury. Additionally, a natural sEH inhibitor luteolin from Inula japonica displayed a pulmonary protective effect towards lung injury mediated by PM2.5 as well. Our results are consistent with the sEH message and protein being both a marker and mechanism for PM2.5-induced inflammation, which suggest its potential as a pharmaceutical target for treating diseases of the respiratory system.
以细颗粒物（PM2.5）为代表的空气污染与呼吸系统疾病密切相关。虽然其机制的认识有限，但肺部炎症与 PM2.5 介导的肺损伤密切相关。可溶性环氧化物水解酶（sEH）和环氧化物脂肪酸在炎症中起着至关重要的作用。在这里，我们试图使用氧化脂质组学来分析 PM2.5 介导的小鼠模型中氧化脂质与肺损伤的关系，发现细胞色素 P450 氧化酶/sEH 介导的代谢途径参与了肺损伤。此外，在肺损伤小鼠中发现 sEH 过表达。有趣的是，sEH 基因缺失或选择性 sEH 抑制剂 TPPU 增加了肺损伤小鼠中环氧化二十碳三烯酸（EETs）的水平，并通过 MAPK/NF-κB 通路使肺巨噬细胞失活，从而防止 PM2.5 介导的肺损伤。此外，来自旋覆花的天然 sEH 抑制剂木犀草素对 PM2.5 介导的肺损伤也具有肺保护作用。我们的结果与 sEH 信使和蛋白质既是 PM2.5 诱导炎症的标志物又是其机制的结果一致，这表明其作为治疗呼吸系统疾病的药物靶点的潜力。
