Melatonin attenuates hepatic ischemia-reperfusion injury in rats by inhibiting NF-κB signaling pathway

Background:The sterile inflammatory response is one of the key mechanisms leading to hepatic ischemia-reperfusion injury.Melatonin has been shown to prevent organ injuries,but its roles in the inflammatory response after hepatic ischemia-reperfusion injury have not been fully explored,especially in late ischemia-reperfusion injury.The present study aimed to investigate the roles and possible mechanisms of melatonin in the inflammatory response after hepatic ischemia-reperfusion injury.Methods:Sixty Sprague-Dawley rats were randomly divided into a sham group,ischemia-reperfusion injury group(I/R group),and melatonin-treated group(M+I/R group).The rats in the I/R group were subjected to 70%hepatic ischemia for 45 min,followed by 5 or 24 h of reperfusion.The rats in the M+I/R group were injected with melatonin(10 mg/kg,intravenous injection)15 min prior to ischemia and immediately before reperfusion.Serum and samples of ischemic liver lobes were harvested for future analysis,and the 7-day survival rate was assessed after hepatic ischemia-reperfusion surgery.Results:In comparison with the I/R group,the M+I/R group showed markedly decreased expression levels of inflammatory cytokines(IL-6 and TNF-α)and numbers of apoptotic hepatocytes(P<0.05).Immunoblotting showed that the expression levels of IL-6,p-NF-κBp65/t-NF-κBp65 and p-IκB-α/t-IκB-αin the M+I/R group were significantly lower than those in the I/R group,and immunofluorescence staining showed that the expression level of p-NF-κBp65 in the M+I/R group was lower than that in the I/R group(P<0.05).The 7-day survival rates were 20%in the I/R group and 50%in the M+I/R group(P<0.05).Conclusions:Melatonin downregulated the activity of the NF-κB signaling pathway in the early and late stages of hepatic ischemia-reperfusion injury,alleviated the inflammatory response,protected the liver from ischemia-reperfusion injury,and increased the survival rate.