Progress of Heme Oxygenase-1 Mediated Ferroptosis in Non-alcoholic Fatty Liver Disease

doi:10.12114/j.issn.1007-9572.2023.0266

Abstract

Abstract:

Ferroptosis plays an important role in the progression of non-alcoholic fatty liver disease (NAFLD) as a novel mode of programmed cell death. Heme oxygenase-1 (HO-1), acting as an inducible oxidase, has been shown the capability of alleviating oxidative stress and hepatocyte necrosis to prevent or delay the progression of NAFLD. However, the mechanism of HO-1 regulating ferroptosis and affecting the development of NAFLD remains inadequately explored. This review provided a systematic and comprehensive summary of the effects of HO-1 on NAFLD by regulating ferroptosis, and discussed the mechanism of HO-1 in preventing the development of NAFLD by summarizing the relevant literature in recent years, and showed that HO-1 regulates ferroptosis in NAFLD through the generation of antioxidants (such as bilirubin and CO), activation of the System Xc, and facilitation of ferrous ion accumulation, in order to provide a theoretical basis for targeting HO-1 gene therapy for NAFLD by methods such as pharmacological interventions and provide a reference for further research.

Key words: Non-alcoholic fatty liver disease, Heme oxygenase-1, Ferroptosis, Review

摘要：

铁死亡是一种新型的细胞程序性死亡方式，在非酒精性脂肪性肝病（NAFLD）进展中发挥重要作用。研究表明，作为一种诱导型氧化酶，血红素氧合酶1（HO-1）可以对抗氧化应激反应、抑制肝细胞坏死等，阻止或延缓NAFLD的进展。但HO-1如何通过调控铁死亡的发生进而影响NAFLD发生、发展的作用机制研究甚少。本文通过归纳近年来相关文献，系统、全面地总结了HO-1通过调控铁死亡的发生对NAFLD的影响，探讨了HO-1阻止NAFLD发生及进展的作用机制。本文表明，在NAFLD中，HO-1分别从合成抗氧化物（包括胆红素、一氧化碳等）、激活System Xc系统、促进亚铁离子的蓄积等方面调控铁死亡，以期为药物干预等方法靶向性HO-1基因治疗NAFLD提供理论依据，并为NAFLD的深入研究提供借鉴。

关键词: 非酒精性脂肪性肝病, 血红素氧合酶1, 铁死亡, 综述

CLC Number:

R 575.5

CAO Jiacen,ZHANG Hongkun,ZHAO Wen, et al. Progress of Heme Oxygenase-1 Mediated Ferroptosis in Non-alcoholic Fatty Liver Disease[J]. Chinese General Practice, 2024, 27(14): 1782-1788. DOI: 10.12114/j.issn.1007-9572.2023.0266.
曹佳岑,张宏坤,赵文等. 血红素氧合酶1调节铁死亡在非酒精性脂肪性肝病中的研究进展[J]. 中国全科医学, 2024, 27(14): 1782-1788. DOI: 10.12114/j.issn.1007-9572.2023.0266.

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