Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, School of Medicine, First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
Kidney Disease Center, College of Medicine, First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
J Cell Mol Med. 2019 Nov;23(11):7151-7162. doi: 10.1111/jcmm.14634. Epub 2019 Sep 2.
The liver is composed of hepatocytes, cholangiocytes, Kupffer cells, sinusoidal endothelial cells, hepatic stellate cells (HSCs) and dendritic cells; all these functional and interstitial cells contribute to the synthesis and secretion functions of liver tissue. However, various hepatotoxic factors including infection, chemicals, high-fat diet consumption, surgical procedures and genetic mutations, as well as biliary tract diseases such as sclerosing cholangitis and bile duct ligation, ultimately progress into liver cirrhosis after activation of fibrogenesis. Melatonin (MT), a special hormone isolated from the pineal gland, participates in regulating multiple physiological functions including sleep promotion, circadian rhythms and neuroendocrine processes. Current evidence shows that MT protects against liver injury by inhibiting oxidation, inflammation, HSC proliferation and hepatocyte apoptosis, thereby inhibiting the progression of liver cirrhosis. In this review, we summarize the circadian rhythm of liver cirrhosis and its potential mechanisms as well as the therapeutic effects of MT on liver cirrhosis and earlier-stage liver diseases including liver steatosis, nonalcoholic fatty liver disease and liver fibrosis. Given that MT is an antioxidative and anti-inflammatory agent that is effective in eliminating liver injury, it is a potential agent with which to reverse liver cirrhosis in its early stage.
肝脏由肝细胞、胆管细胞、库普弗细胞、肝窦内皮细胞、肝星状细胞（HSCs）和树突状细胞组成；所有这些功能和间质细胞都有助于肝脏组织的合成和分泌功能。然而，包括感染、化学物质、高脂肪饮食摄入、手术程序和基因突变在内的各种肝毒性因素，以及硬化性胆管炎和胆管结扎等胆道疾病，在纤维发生激活后最终进展为肝硬化。褪黑素（MT）是从松果体中分离出来的一种特殊激素，参与调节多种生理功能，包括促进睡眠、昼夜节律和神经内分泌过程。现有证据表明，MT 通过抑制氧化、炎症、HSC 增殖和肝细胞凋亡来保护肝脏免受损伤，从而抑制肝硬化的进展。在这篇综述中，我们总结了肝硬化的昼夜节律及其潜在机制，以及 MT 对肝硬化和早期肝脏疾病（包括肝脂肪变性、非酒精性脂肪性肝病和肝纤维化）的治疗作用。鉴于 MT 是一种抗氧化和抗炎剂，可有效消除肝损伤，因此它是一种具有逆转早期肝硬化潜力的药物。
