Effect of Soluble Epoxide Hydrolase in Hyperoxic Acute Lung Injury in Mice

Hyperoxic acute lung injury is a serious complication of oxygen therapy that causes high mortality. Inhibition of soluble epoxide hydrolase (sEH) has been reported to have protective effect on lipopolysaccharide-induced acute lung injury (ALI). This study investigates whether sEH plays any role in the pathogenesis of hyperoxic ALI. Wild-type and sEH gene knockout (sEH(-/-)) mice were exposed to 100% O-2 for 72 h to induce hyperoxic ALI. Hyperoxia caused infiltration of inflammatory cells, elevation of interleukin-1 beta and interleukin-6 levels, and deterioration of alveolar capillary protein leak as well as wet/dry weight ratio in the lung. The hyperoxia-induced pulmonary inflammation and edema were markedly improved in sEH(-/-) mice. Survival rate was significantly improved in sEH(-/-) mice compared with that in wild-type mice. Moreover, the levels of epoxyeicosatrienoic acids and heme oxygenase-1 activity were notably elevated in sEH(-/-) mice compared with those in wild-type mice after exposure to 100% O-2 for 72 h. The nucleotide-binding domains and leucine-rich repeat pyrin domains containing 3 (NLRP3) inflammasome activation and caspase-1 activity induced by hyperoxia were inhibited in sEH(-/-) mice compared with those in wild-type mice. Inhibition of sEH by an inhibitor, AUDA, dampened hyperoxia-induced ALI. sEH plays a vital role in hyperoxic ALI and is a potential therapeutic target for ALI.