核因子E2相关因子2在急性肝损伤中的作用机制与治疗潜力

陶辉跃; 杨娜; 刘杨

doi:10.12449/JCH260127

核因子E2相关因子2在急性肝损伤中的作用机制与治疗潜力

DOI: 10.12449/JCH260127

陶辉跃,
杨娜^, ,,
刘杨^, ,

山西中医药大学基础医学院，山西晋中 030619

基金项目:

山西省科学技术厅山西省重点国别科技合作项目 (202104041101013);

山西中医药大学科技创新团队项目 (2022TD2003);

中西医结合防治风湿免疫病山西省科技创新人才重点团队 (202204051002033);

山西省中医药管理局科研课题 (2024ZYYAD008);

山西省自然科学基金 (202203021222272);

山西中医药大学科技创新能力培育计划国家自然科学基金培育专项 (2024PY-NS-014);

山西省研究生教育创新计划项目（优秀研究生导师团队项目） (2024TD33)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：陶辉跃负责课题设计，资料分析，撰写论文；杨娜参与收集数据，修改论文；刘杨负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
杨娜， yangna@sxtcm.edu.cn （ORCID： 0000-0003-0610-0902）

刘杨， liuyang1980@sxtcm.edu.cn （ORCID： 0000-0002-6627-5002）

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出版历程
- 收稿日期: 2025-04-27
- 录用日期: 2025-09-01
- 出版日期: 2026-01-25

The mechanism and therapeutic potential of nuclear factor erythroid 2-related factor 2 in acute liver injury

Huiyue TAO,
Na YANG^{,
,},
Yang LIU^{,
,}

College of Basic Medical Sciences，Shanxi University of Chinese Medicine，Jinzhong，Shanxi 030619，China

Research funding:

Shanxi Provincial Department of Science and Technology Shanxi Province Key Country Science and Technology Cooperation Project (202104041101013);

Science and Technology Innovation Team Project of Shanxi University of Traditional Chinese Medicine (2022TD2003);

Shanxi Province Key Team of Scientific and Technological Innovation Talents for the Prevention and Treatment of Rheumatic Immunology with Integrated Traditional Chinese and Western Medicine (202204051002033);

Shanxi Provincial Administration of Traditional Chinese Medicine (2024ZYYAD008);

Natural Science Foundation of Shanxi Province (202203021222272);

Shanxi University of Traditional Chinese Medicine Science and Technology Innovation Capacity Development Program National Natural Science Foundation Cultivation Project (2024PY-NS-014);

Shanxi Graduate Education Innovation Program Project（Outstanding Graduate Tutor Team Project） (2024TD33)

More Information

Corresponding author: YANG Na， yangna@sxtcm.edu.cn （ORCID： 0000-0003-0610-0902）; LIU Yang， liuyang1980@sxtcm.edu.cn （ORCID： 0000-0002-6627-5002）

摘要

摘要: 急性肝损伤是严重威胁患者生命安全的疾病，目前尚缺乏理想的治疗方案。核因子E2相关因子2（Nrf2）作为细胞保护转录因子，在急性肝损伤治疗中具有重要潜力。Nrf2通过诱导抗氧化酶表达、调节铁和脂肪酸代谢、保护线粒体功能及抑制炎症反应等机制发挥保护作用；Nrf2通过激活抗氧化响应元件，促进血红素氧合酶1、谷胱甘肽S转移酶、谷氨酰半胱氨酸连接酶等抗氧化酶的表达，增强肝脏的抗氧化能力，从而抑制急性肝损伤发展；Nrf2可调节由不同病因引起的急性肝损伤；姜黄素等天然化合物与奥替普拉等合成化合物可通过不同机制激活Nrf2，增强肝脏抗氧化能力，对急性肝损伤产生保护作用。然而，Nrf2在急性肝损伤治疗中仍面临诸多挑战，作用机制尚未完全阐明，多数仍处于实验研究阶段，未来期望深入研究Nrf2信号通路作用机制，优化药物研发策略，完善激动剂的临床应用理论，为急性肝损伤患者提供更为有效、精准的治疗方案。
- 核因子E2相关因子2 /
- 急性肝损伤 /
- 药理作用分子作用机制
Abstract: Acute liver injury poses a serious threat to the life safety of patients， and currently there is still a lack of satisfactory treatment options. As a cytoprotective transcription factor， nuclear factor erythroid 2-related factor 2 （Nrf2） has important potential in the treatment of acute liver injury. Nrf2 exerts a protective effect by inducing the expression of antioxidant enzymes， regulating iron and fatty acid metabolism， protecting mitochondrial function， and inhibiting inflammatory responses， and it can also enhance the antioxidant capacity of the liver and inhibit the progression of acute liver injury by activating antioxidant response element and promoting the expression of the antioxidant enzymes such as heme oxygenase-1， glutathione transferase， and glutamate-cysteine ligase catalytic subunit. Nrf2 can modulate acute liver injury caused by different etiologies. Natural compounds such as curcumin and synthetic compounds such as oltipraz can activate Nrf2 through different mechanisms， enhance the antioxidant capacity of the liver， and thus exert a protective effect against acute liver injury. However， there are still various challenges in Nrf2 in the treatment of acute liver injury， and its mechanism of action remains unclear， with most studies in the stage of experimental study. In the future， it is expected to deeply investigate the mechanism of action of the Nrf2 signaling pathway， optimize drug development strategies， improve the clinical application theories for agonists， and provide more effective and precise treatment regimens for patients with acute liver injury.
- Nuclear Factor-Erythroid 2-Related Factor 2 /
- Acute Liver Injury /
- Molecular Mechanisms of Pharmacological Action

HTML全文

注： Nrf2，核因子E2相关因子2；Keap1，Kelch样ECH相关蛋白1；ROS，活性氧；ARE，抗氧化响应元件；HO-1，血红素氧合酶1；Heme，血红素；GST，谷胱甘肽S转移酶；GSH，谷胱甘肽；Fe²⁺，二价铁离子；CO，一氧化碳；BV，胆绿素。

图 1 氧化还原信号中的Nrf2/HO-1/GST信号通路

Figure 1. Nrf2/HO-1/GST signaling pathway in redox signaling

下载: 全尺寸图片幻灯片

注： LPS，脂多糖；TLR4，Toll样受体4；TNF-α，肿瘤坏死因子-α；IL-6，白细胞介素-6；Nrf2，核因子E2相关因子2；GCLC，谷氨酰半胱氨酸连接酶。

图 2 Nrf2/GCLC信号通路

Figure 2. Nrf2/GCLC signaling pathway

下载: 全尺寸图片幻灯片

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核因子E2相关因子2在急性肝损伤中的作用机制与治疗潜力

DOI: 10.12449/JCH260127

通信作者:
杨娜， yangna@sxtcm.edu.cn （ORCID： 0000-0003-0610-0902）

刘杨， liuyang1980@sxtcm.edu.cn （ORCID： 0000-0002-6627-5002）

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The mechanism and therapeutic potential of nuclear factor erythroid 2-related factor 2 in acute liver injury

Corresponding author: YANG Na， yangna@sxtcm.edu.cn （ORCID： 0000-0003-0610-0902）; LIU Yang， liuyang1980@sxtcm.edu.cn （ORCID： 0000-0002-6627-5002）

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核因子E2相关因子2在急性肝损伤中的作用机制与治疗潜力

DOI: 10.12449/JCH260127

通信作者: 杨娜， yangna@sxtcm.edu.cn （ORCID： 0000-0003-0610-0902） 刘杨， liuyang1980@sxtcm.edu.cn （ORCID： 0000-0002-6627-5002）

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The mechanism and therapeutic potential of nuclear factor erythroid 2-related factor 2 in acute liver injury

Corresponding author: YANG Na， yangna@sxtcm.edu.cn （ORCID： 0000-0003-0610-0902）; LIU Yang， liuyang1980@sxtcm.edu.cn （ORCID： 0000-0002-6627-5002）

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通信作者:
杨娜， yangna@sxtcm.edu.cn （ORCID： 0000-0003-0610-0902）

刘杨， liuyang1980@sxtcm.edu.cn （ORCID： 0000-0002-6627-5002）