PPARγ Mediates Protective Effect against Hepatic Ischemia/Reperfusion Injury via NF-κB Pathway

Background: Hepatic ischemia/reperfusion injury (HIRI) is an unavoidable complication in liver surgery, however its pathological process is still unclear. Therefore, in this study, the role and mechanism of peroxisome proliferator-activated receptor gamma (PPAR gamma) was investigated in HIRI. Materials and Methods: We constructed mice models with HIRI and L02 cell models insulted hypoxia/re-oxygenation (H/R). PPAR gamma agonist rosiglitazone was administered prior to HIRI in mice and PPAR gamma-siRNA was to H/R treatment in L02 cells. Liver injury was measured by serum ALT, AST and LDH levels and performing H&E staining; the inflammatory injury was reflected by inflammatory markers IL-1 beta, IL-6 and TNF-alpha, which were assayed by Real-time PCR and Western blotting, MPO activity was determined using commercial kits; oxidative stress injury was evaluated by iNOS, MDA, SOD and GSH-PX levels; apoptosis was detected by cleaved-Caspase-3, TUNEL staining and flow cytometry; NF-kappa B signaling activation was reflected by phosphorylation of I kappa B alpha (p-I kappa B alpha) and nuclear translocation of NF-kappa B p65. Results: The level of PPAR gamma expression was obviously down-regulated both in mice liver subjected to IRI and in L02 cells to H/R. Overexpression of PPAR gamma presented protective effect on HIRI by reducing serum levels of aminotransferase and hepatic necrosis, inhibiting inflammation and apoptosis and alleviating oxidative stress in vivo. But PPAR gamma-siRNA aggravate H/R insult by promoting inflammation and apoptosis in vitro. Mechanistically, the NF-kappa B pathway activity was increased with PPAR gamma down-regulation by PPAR gamma-siRNA. Importantly, inhibition of NF-kappa B signaling abolished PPAR gamma knockdown-mediated hepatic injury. Conclusions: PPAR gamma present protective effects on HIRI by attenuating liver injury, inflammatory response, oxidative stress and apoptosis in vivo and in vitro, and its mechanism may be related to down-regulation of NF-kappa B signaling.