Soluble epoxide hydrolase inhibitor 1-trifluoromethoxyphenyl-3- (1-propionylpiperidin-4-yl) urea attenuates bleomycin-induced pulmonary fibrosis in mice

摘要: Epoxyeicosatrienoic acids (EETs), the metabolites of arachidonic acid derived from cytochrome P450 (CYP450) epoxygenases, are mainly metabolized by soluble epoxide hydrolase (sEH) to their corresponding diols. EETs but not diols, have anti-inflammatory properties and inhibition sEH might provide protective effects against inflammatory fibrosis. We test a selected inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), on bleomycin-induced pulmonary fibrosis (PF) in mice. A mouse model PF was established intratracheal injection bleomycin TPPU administered for 21 days after injection. found treatment improved body weight loss survival rate bleomycin-stimulated Histological examination showed that alleviated inflammation maintained alveolar structure tissues. also decreased deposition collagen expression procollagen I mRNA lung tissues transforming growth factor-β1 (TGF-β1), interleukin-1β (IL-1β) IL-6 levels serum Furthermore, inhibited proliferation synthesis fibroblasts partially reversed TGF-β1-induced α-smooth muscle actin expression. Our results indicate attenuates therefore prevents model.