Effect of Soluble Epoxide Hydrolase in Hyperoxic Acute Lung Injury in Mice
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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% O2 for 72 h to induce hyperoxic ALI. Hyperoxia caused infiltration of inflammatory cells, elevation of interleukin-1β 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% O2 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.
KEY WORDSsoluble epoxide hydrolase hyperoxia acute lung injury inflammation
We thank Sun Liu and Xuan Jiang for critical reading of the manuscript, and Qin Xiao and Yue-Xiang Chen for technical assistance.
PSL, WT, and YSS conceived and designed the experiments.
WT and LQY performed the experiments.
WT and LQY analyzed data.
WT drafted the manuscript.
LQY edited and revised the manuscript.
PSL and WT interpreted results of the experiments.
PSL, WT, LQY, and YSS approved the final version of the manuscript.
Compliance with Ethical Standards
All studies were performed in accordance with the National Institutes of Health guidelines for the use of experimental animals. The current project was approved by the Ethics Committee of Animal Research of Yangzhou University.
Conflict of Interest
The authors declare that they have no conflict of interest.
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