State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Cell Prolif. 2021 Apr;54(4):e13021. doi: 10.1111/cpr.13021. Epub 2021 Mar 10.
Although the liver is the only organ with regenerative capacity, various injury factors induce irreversible liver dysfunction and end-stage liver disease. Liver resection and liver transplantation (LT) are effective treatments for individuals with liver failure, liver cirrhosis and liver cancers. The remnant or transplanted liver tissues will undergo hepatic ischaemia/reperfusion (IR), which leads to oxidative stress, inflammation, immune injury and liver damage. Moreover, systemic ischaemia induced by trauma, stroke, myocardial ischaemia, haemorrhagic shock and other injury factors also induces liver ischaemia/reperfusion injury (IRI) in individuals. Hepatic IRI can be divided into warm IRI, which is induced by liver surgery and systemic ischaemia, and cold IRI, which is induced by LT. Multiple studies have shown that melatonin (MT) acts as an endogenous free radical scavenger with antioxidant capacity and is also able to attenuate hepatic IRI via its anti-inflammatory and antiapoptotic capacities. In this review, we discuss the potential mechanisms and current strategies of MT administration in liver surgery for protecting against warm or cold hepatic IRI. We highlight strategies to improve the efficacy and safety of MT for attenuating hepatic IRI in different conditions. After the potential mechanisms underlying the interactions between MT and other important cellular processes during hepatic IR are clarified, more opportunities will be available to use MT to treat liver diseases in the future.
虽然肝脏是唯一具有再生能力的器官，但各种损伤因素可导致不可逆转的肝功能障碍和终末期肝病。肝切除术和肝移植（LT）是治疗肝功能衰竭、肝硬化和肝癌患者的有效方法。残余或移植的肝组织会经历肝缺血/再灌注（IR），导致氧化应激、炎症、免疫损伤和肝损伤。此外，创伤、中风、心肌缺血、失血性休克和其他损伤因素引起的全身缺血也会导致个体的肝缺血/再灌注损伤（IRI）。肝IRI 可分为由肝手术和全身缺血引起的热缺血再灌注损伤，以及由 LT 引起的冷缺血再灌注损伤。多项研究表明，褪黑素（MT）作为一种内源性自由基清除剂，具有抗氧化能力，通过其抗炎和抗凋亡作用来减轻肝 IRI。在这篇综述中，我们讨论了 MT 在肝外科手术中预防热或冷肝 IRI 的潜在机制和当前策略。我们强调了改善 MT 在不同情况下减轻肝 IRI 的疗效和安全性的策略。阐明 MT 与肝 IR 期间其他重要细胞过程相互作用的潜在机制后，将来将有更多机会使用 MT 治疗肝脏疾病。
