The Protective Effect of EET on Renal I/R through NLRP3 and Pyroptosis

With the increasing morbidity and mortality of renal ischemia/reperfusion, whether epoxyeicosatrienoic acids could protect against it and the relative mechanism needs further exploration. Aim: To investigate the effect of epoxyeicosatrienoic acids on renal ischemia/reperfusion injury. Methods: Thirty mice were randomly divided into sham group, ischemia/reperfusion group, ischemia/reperfusion with epoxyeicosatrienoic acids group, ischemia/reperfusion with toll-like receptor 4 inhibitor group, ischemia/reperfusion with epoxyeicosatrienoic acids and toll-like receptor 4 inhibitor group. Kidney function and pathology changes were observed 24 h after surgery. ELISA was used to exam the level of serum interleukin1β, tumor necrosis factor α and nod-like receptor 3. The protein expression of nod-like receptor 3, cleaved cysteinyl aspartate specific proteinase 1, pro-interleukin-1β, interleukin-1β, toll-like receptor 4 and nuclear factor kappa-light-chain-enhancer of activated B cells p65 were evaluated by western blot. Result: Compared with the sham group, the ischemia/reperfusion group showed severe renal tubular epithelial cell necrosis (P<0.05). BUN, Scr and interleukin-1β, tumor necrosis factor α, nod-like receptor 3, toll-like receptor 4, cleaved cysteinyl aspartate specific proteinase 1 were obviously higher than those in the sham group (P<0.05). Furthermore, epoxyeicosatrienoic acids were alleviated in the ischemia/reperfusion-induced kidney function damage and expression of above protein (P<0.05), the level of each proteins was significantly reduced after the co-administration of toll-like receptor 4 inhibitor and epoxyeicosatrienoic acids (P<0.05). Conclusion: Epoxyeicosatrienoic acids can reduce renal ischemia/reperfusion injury, and its mechanism may be related to the regulation of nod-like receptor 3 production and pyroptosis through the toll-like receptor 4 pathway.