Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.