Recent studies reported that soluble epoxide hydrolase (sEH) plays an important role in lung diseases. However, the role of sEH in hyperoxia-induced ALI is unclear.
ALI was induced by exposure to 100% oxygen in an airtight cage for 72 h in wild-type (WT) and sEH gene deletion (EPHX2−/−) mice. ALI was assessed by the lung dry/wet ratio, alveolar capillary protein leak, and the infiltration of inflammatory cells in the lung.
Hyperoxia elevated sEH activity in WT mice. Simultaneously, epoxyeicosatrienoic acids (EETs) levels were decreased in WT mice exposed to hyperoxia. However, the level of EETs was increased in EPHX2−/− mice exposed to hyperoxia. Hyperoxia induced pulmonary edema and inflammation were dampened in EPHX2−/− mice compared with WT mice. Decreased expression of Kelch-like ECH-associated protein 1 (Keap1) was found in EPHX2−/− mice exposed to hyperoxia. Hyperoxia-induced the expression of nuclear-factor erythroid 2-related factor 2 (Nrf2) was enhanced in EPHX2−/− mice compared with WT mice. Simultaneously, the activities of heme oxygenase-1 and superoxide dismutase were elevated in EPHX2−/− mice. The levels of reactive oxygen species were inhibited in EPHX2−/− mice compared with WT mice exposed to hyperoxia.
sEH is a harmful factor for hyperoxic ALI. The beneficial effect of sEH gene deletion is associated with the elevation of EETs and regulation of Nrf2/Keap1 signal pathway.