Gao Yao, Li Zhi-Tao, Jin Li, Lin Jie, Fan Zheng-Lei, Zeng Zhong, Huang Han-Fei
Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
Hepatobiliary Pancreat Dis Int. 2021 Dec;20(6):551-560. doi: 10.1016/j.hbpd.2021.04.001. Epub 2021 Apr 18.
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.
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.
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).
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.
无菌性炎症反应是导致肝缺血再灌注损伤的关键机制之一。褪黑素已被证明可预防器官损伤，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研究，尤其是在晚期缺血再灌注损伤中。本研究旨在探讨褪黑素在肝缺血再灌注损伤后炎症反应中的作用及可能机制。
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组大鼠进行70%肝缺血45分钟，随后再灌注5或24小时。M + I/R组大鼠在缺血前15分钟和再灌注前即刻静脉注射褪黑素（10mg/kg）。采集血清和缺血肝叶样本用于后续分析，并在肝缺血再灌注手术后评估7天生存率。
与I/R组相比，M + I/R组炎症细胞因子（IL-6和TNF-α）表达水平及凋亡肝细胞数量明显降低（P < 0.05）。免疫印迹显示，M + I/R组中IL-6、p-NF-κBp65/t-NF-κBp65和p-IκB-α/t-IκB-α的表达水平明显低于I/R组，免疫荧光染色显示M + I/R组中p-NF-κBp65的表达水平低于I/R组（P < 0.05）。I/R组7天生存率为20%，M + I/R组为50%（P < 0.
