慢性代谢性肝病氧化应激研究新进展

摘要/Abstract

摘要： 肝脏作为人体的重要脏器之一,在体内以代谢功能为主,具有去氧化、储存肝糖、合成分泌性蛋白质等重要功能。肝脏长期暴露于活性氧下,当体内活性氧积累过多使氧化与抗氧化平衡失调时,则会引起肝细胞受损。无论在生理还是病理状态下,氧化应激都在肝脏中承担重要角色,而氧化与抗氧化失衡程度则决定慢性肝病的病情进展。本文从氧化应激途径对慢性代谢性肝病不同阶段重要氧化应激调控通路调控,以及慢性代谢性肝病疾病进程的影响展开综述。

关键词: 慢性肝病, 氧化应激, 铁死亡, Keap1-Nrf2-ARE

张楠, 郑顺, 赵晨兴, 杨躍鑫, 徐文静. 慢性代谢性肝病氧化应激研究新进展[J]. 肝脏, 2025, 30(12): 1735-1738.

/ 推荐

参考文献

[1] He Q, He W, Dong H, et al. Role of liver sinusoidal endothelial cell in metabolic dysfunction-associated fatty liver disease [J]. Cell Commun Signal, 2024, 22(1): 346-64.
[2] Cabral F, Al-Rahem M, Skaggs J, et al. Stabilin receptors clear LPS and control systemic inflammation [J]. iScience, 2021, 24(11): 103337.
[3] He F, Ru X, Wen T. NRF2, a transcription factor for stress response and beyond [J]. Int J Mol Sci, 2020, 21(13):4777-4800.
[4] Jiang X, Stockwell B R, Conrad M. Ferroptosis: mechanisms, biology and role in disease [J]. Nat Rev Mol Cell Biol, 2021, 22(4): 266-282.
[5] Dixon S J, Lemberg K M, Lamprecht M R, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death [J]. Cell, 2012, 149(5): 1060-1072.
[6] Zhang Y, Li M, Guo Y, et al. The organelle-specific regulations and epigenetic regulators in ferroptosis [J]. Front Pharmacol, 2022, 13: 905501.
[7] Addo L, Tanaka H, Yamamoto M, et al. Hepatic nerve growth factor induced by iron overload triggers defenestration in liver sinusoidal endothelial cells [J]. Biochim Biophys Acta, 2015, 1852(1): 175-183.
[8] Biquard L, Rautou P E. Autophagy and extracellular vesicles in the liver endothelium: friends or foes? [J]. Hepatol Int, 2024, 18(1): 1-3.
[9] Ramani K, Mavila N, Abeynayake A, et al. Correction: targeting A-kinase anchoring protein 12 phosphorylation in hepatic stellate cells regulates liver injury and fibrosis in mouse models [J]. Elife, 2023, 12:e88586.
[10] Chen H, Zhao W, Yan X, et al. Overexpression of hepcidin alleviates steatohepatitis and fibrosis in a diet-induced nonalcoholic steatohepatitis [J]. J Clin Transl Hepatol, 2022, 10(4): 577-588.
[11] Gao H, Jin Z, Bandyopadhyay G, et al. Aberrant iron distribution via hepatocyte-stellate cell axis drives liver lipogenesis and fibrosis [J]. Cell Metab, 2022, 34(8): 1201-1213.e5.
[12] Yang Y, Wang Y, Guo L, et al. Interaction between macrophages and ferroptosis [J]. Cell Death Dis, 2022, 13(4): 355-365.
[13] Jiang Q, Wan R, Jiang J, et al. Interaction between macrophages and ferroptosis: metabolism, function, and diseases [J]. Chin Med J (Engl), 2024, 138(5): 509-522.
[14] Zeng J, Qin L, Jin Q, et al. Prevalence and characteristics of MAFLD in Chinese adults aged 40 years or older: a community-based study [J]. Hepatobiliary Pancreat Dis Int, 2022, 21(2): 154-161.
[15] Rinella M E, Neuschwander-Tetri B A, Siddiqui M S, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease [J]. Hepatology, 2023, 77(5): 1797-1835.
[16] Imarisio C, Alchera E, Bangalore Revanna C, et al. Oxidative and ER stress-dependent ASK1 activation in steatotic hepatocytes and Kupffer cells sensitizes mice fatty liver to ischemia/reperfusion injury [J]. Free Radic Biol Med, 2017, 112: 141-148.
[17] Liu S, Zhang L, Xu J, et al. Identification of Ferroptosis -Related Genes in MAFLD/MASH and HQHF Validation [J]. Hepat Med, 2025, 17: 13-24.
[18] Jian Y, Li Y, Zhou Y, et al. Pollutants in microenvironmental cellular interactions during liver inflammation cancer transition and the application of multi-omics analysis [J]. Toxics, 2025, 13(3):163-179.
[19] Wan L Y, Peng H, Ni Y R, et al. The miR-23b/27b/24-1 cluster inhibits hepatic fibrosis by inactivating hepatic stellate cells [J]. Cell Mol Gastroenterol Hepatol, 2022, 13(5): 1393-1412.
[20] Duan L, Yao Y, Kong H, et al. Chemokines and chemokine receptors: potential therapeutic targets in systemic lupus erythematosus [J]. Cytokine, 2024, 184: 156770.
[21] Du Z, Lin Z, Wang Z, et al. SPOCK1 overexpression induced by platelet-derived growth factor-BB promotes hepatic stellate cell activation and liver fibrosis through the integrin α5β1/PI3K/Akt signaling pathway [J]. Lab Invest, 2020, 100(8): 1042-1056.
[22] Glässner A, Eisenhardt M, Krämer B, et al. NK cells from HCV-infected patients effectively induce apoptosis of activated primary human hepatic stellate cells in a TRAIL-, FasL- and NKG2D-dependent manner [J]. Lab Invest, 2012, 92(7): 967-977.
[23] Hassannia B, Vandenabeele P, Vanden Berghe T. Targeting ferroptosis to iron out cancer [J]. Cancer Cell, 2019, 35(6): 830-849.
[24] Vechalapu S K, Kumar R, Sachan S K, et al. Copper and manganese complexes of pyridinecarboxaldimine induce oxidative cell death in cancer cells [J]. ACS Appl Bio Mater, 2024, 7(10): 6696-6705.
[25] Suthiram K T, Ghazi T, Abdul N S, et al. Kojic acid induces oxidative stress and anti-inflammatory effects in human hepatocellular carcinoma (HepG2) cells [J]. Toxicon, 2023, 232: 107221.
[26] Mohammadian K, Fakhar F, Keramat S, et al. The role of antioxidants in the treatment of metabolic dysfunction-associated fatty liver disease: a systematic review [J]. Antioxidants (Basel), 2024, 13(7):797-836.
[27] Yu C, Xu Y, Zhao M, et al. New insights into mechanism of ellagic acid alleviating arsenic-induced oxidative stress through MAPK/keap1-Nrf2 signaling pathway response, molecular docking and metabolomics analysis in HepG2 cells [J]. Ecotoxicol Environ Saf, 2024, 285: 117029.
[28] Khadrawy S M, Mohamed H M, Mahmoud A M. Mesenchymal stem cells ameliorate oxidative stress, inflammation, and hepatic fibrosis via Nrf2/HO-1 signaling pathway in rats [J]. Environ Sci Pollut Res Int, 2021, 28(2): 2019-2030.
[29] Li N, Wang R, Ai X, et al. Electroacupuncture inhibits neural ferroptosis in rat model of traumatic brain injury via activating system Xc(-)/GSH/GPX4 Axis [J]. Curr Neurovasc Res, 2024, 21(1): 86-100.
[30] Meng F, Xiao Y, Ji Y, et al. An open-like conformation of the sigma-1 receptor reveals its ligand entry pathway [J]. Nat Commun, 2022, 13(1): 1267-1278.
[31] Wu Z, Khodade V S, Chauvin J R, et al. Hydropersulfides inhibit lipid peroxidation and protect cells from ferroptosis [J]. J Am Chem Soc, 2022, 144(34): 15825-15837.
[32] Lu C, Xu C, Li S, et al. Liraglutide and GLP-1(9-37) alleviated hepatic ischemia-reperfusion injury by inhibiting ferroptosis via GSK3β/Nrf2 pathway and SMAD159/Hepcidin/FTH pathway [J]. Redox Biol, 2025, 79: 103468.
[33] Sun D, Wang L, Wu Y, et al. Lipid metabolism in ferroptosis: mechanistic insights and therapeutic potential [J]. Front Immunol, 2025, 16: 1545339.