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-α in 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.

中文翻译：

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褪黑素通过抑制 NF-κB 信号通路减轻大鼠肝脏缺血再灌注损伤

背景

无菌性炎症反应是导致肝脏缺血再灌注损伤的关键机制之一。褪黑激素已被证明可以预防器官损伤，但其在肝缺血再灌注损伤后炎症反应中的作用尚未得到充分探索，特别是在晚期缺血再灌注损伤中。本研究旨在探讨褪黑激素在肝缺血再灌注损伤后炎症反应中的作用及其可能机制。

方法

将60只Sprague-Dawley大鼠随机分为假手术组、缺血再灌注损伤组（I/R组）和褪黑素治疗组（M+I/R组）。I/R组大鼠70%肝缺血45 min，再灌注5或24 h。M+I/R组大鼠在缺血前15分钟和再灌注前立即注射褪黑激素（10mg/kg，静脉注射）。收集缺血性肝叶的血清和样本以供将来分析，并评估肝缺血再灌注手术后的 7 天存活率。

结果

与I/R组比较，M+I/R组炎性细胞因子（IL-6和TNF-α）的表达水平和凋亡肝细胞的数量显着降低（P  < 0.05）。免疫印迹显示，M+I/R组IL-6、p-NF-κBp65/t-NF-κBp65和p-IκB-α/t-IκB-α的表达水平显着低于I组。 /R组，免疫荧光染色显示，M+I/R组p-NF-κBp65表达水平低于I/R组（P  < 0.05）。I/R组7天生存率为20%，M+I/R组为50%（P  <0.05）。

结论

褪黑激素在肝脏缺血再灌注损伤早期和晚期下调NF-κB信号通路的活性，减轻炎症反应，保护肝脏免受缺血再灌注损伤，提高存活率。