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| Melatonin attenuates hepatic ischemia-reperfusion injury in rats by inhibiting NF-κB signaling pathway |
| Yao Gao, Zhi-Tao Li, Li Jin, Jie Lin, Zheng-Lei Fan, Zhong Zeng, Han-Fei Huang ∗ |
Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China
∗ Corresponding author.
E-mail address: kmhhf@126.com (H.-F. Huang). |
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Abstract 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-I κB- α/t-I κB- 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.
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2021, Vol. 20 
