[Implications of EET in renal ischemia/reperfusion by regulating NLRP3 expression and pyroptosis].

Objective: To investigate the mechanism of epoxyeicosatrienoic acids (EET) on renal ischemia/reperfusion (I/R). Methods: Thirty 10-week male C57BL6 mice were randomly divided into five groups: sham goup, I/R group, I/R with EET group, I/R with toll-like receptor 4 (TLR4) inhibitor (TAK242) group, I/R with EET and TAK242 group. Blood urea nitrogen (BUN) and serum creatinine (Scr) as well as renal pathological changes were observed 24 h after reperfusion. The protein expression of NOD-like receptor pyrin domain containing 3 (NLRP3), cysteinyl aspartate specific proteinase 1 (caspase-1), interleukin-1beta (IL-1beta), TLR4 and myeloid differentiation factor 88 (MyD88) were evaluated using Western blot. Results: Severe renal tubular epithelial cell injury and decreased renal function [BUN:(10.37+/-0.53) vs (6.70+/-0.82)mmol/L, t=9.17, P<0.001; Scr: (83.67+/-3.88) vs (32.50+/-3.51)mumol/L, t=23.96, P<0.001] occurred in I/R group. Compared to the sham group, the relative expression of NLRP3 (1.54+/-0.10 vs 0.71+/-0.05, t=13.14, P<0.001), caspase-1 (2.35+/-0.05 vs 0.62+/-0.02, t=73.77, P<0.001), IL-1beta (3.11+/-0.11 vs 1.26+/-0.05, t=35.97, P<0.001), TLR4 (1.58+/-0.03 vs 0.39+/-0.01, t=86.00, P<0.001), MyD88 (0.94+/-0.02 vs 0.26+/-0.01, t=72.61, P<0.001) were significantly increased. Mice pretreated with EET analog featured lower kidney damage and diminished levels of above proteins than I/R group (all P<0.001). Besides, the co-administration of TAK242 and EET analog could even markedly reduced the expression levels of each proteins than those in I/R group and I/R with EET group (all P<0.001). Conclusion: EET exerts a protective effect on attenuating renal I/R injury possibly through inhibiting TLR4 pathway to regulate the activation of NLRP3-induced pyroptosis.