昼夜节律与肝损伤

doi:10.6040/j.issn.1671-7554.0.2026.0952

Abstract

Abstract: Circadian rhythm is an endogenous timekeeping system that enables organisms to adapt to light-dark cycles, feeding rhythms and environmental changes. At the molecular level, circadian oscillation is maintained by transcriptional-translational feedback loops composed of clock circadian regulator(CLOCK), basic helix-loop-helix ARNT like 1(BMAL1), period(PER), cryptochrome(CRY), REV-ERB nuclear receptor(REV-ERB)and retinoic acid receptor-related orphan receptor(ROR). The liver is a central organ for metabolism, detoxification and immune regulation, and also a typical peripheral clock organ. Hepatic glucose and lipid metabolism, bile acid synthesis, xenobiotic metabolism, mitochondrial oxidative phosphorylation, antioxidant defense and immune responses exhibit robust circadian oscillations. Accumulating evidence indicates that circadian disruption contributes to a variety of liver injury-related disorders, including metabolic dysfunction-associated steatotic liver disease, drug-induced liver injury, alcoholic liver disease, cholestatic liver injury, hepatic ischemia/reperfusion injury and liver fibrosis. Mechanistically, circadian clocks regulate liver injury by modulating insulin resistance, oxidative stress, inflammatory responses, autophagy, endoplasmic reticulum stress and multiple forms of regulated cell death. Conversely, hepatic injury-associated lipid accumulation, hypoxia, inflammatory cytokine release and metabolic reprogramming may disturb local hepatic clocks, forming a vicious cycle of circadian disruption, metabolic imbalance and aggravated liver injury. This review summarized the molecular basis of circadian rhythm and its role in hepatic metabolic homeostasis, highlighted the mechanistic links between circadian clocks and liver injury, and discussed potential therapeutic strategies based on chronobiology.

Key words: Circadian rhythm, Liver injury, Hepatic metabolism, Insulin resistance, Inflammation, Cell death, Chronopharmacology

CLC Number:

R575

QU Zetong, MA Chunhong. Circadian rhythm and liver injury[J].Journal of Shandong University (Health Sciences), 2026, 64(10): 1-15.

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