代谢相关脂肪性肝病中内质网应激与铁死亡的关系

史良; 常占杰; 闫春潇; 焦俊喆; 闫瑞娟; 闫曙光; 李京涛; 张海博

doi:10.12449/JCH260624

代谢相关脂肪性肝病中内质网应激与铁死亡的关系

DOI: 10.12449/JCH260624

1.
陕西中医药大学中医学院，陕西咸阳 712046
2.
陕西中医药大学附属医院肝病医院一病区，陕西咸阳 712000
3.
陕西中医药大学基础医学院，陕西咸阳 712046

基金项目:

国家自然科学基金 (82174330);

国家自然科学基金 (82405335);

陕西省教育厅青年创新团队 (25JP049);

陕西省中医药管理局“双链融合”创新团队 (2022-SLRH-LJ-002);

咸阳市重大科技创新专项 (L2023-ZDKJ-CYJQ-SF-011);

陕西中医药大学校级高水平中医药重点学科 (2024XKZD19);

陕西省中医药科研创新人才 (2025-CXRC-19);

陕西中医药大学科技创新人才体系建设计划项目 (2024-KJXX-03)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：史良、闫春潇负责论文主体内容撰写；焦俊喆、闫瑞娟参与文献检索、筛选及初稿修改；常占杰、闫曙光拟定写作思路，指导论文撰写；李京涛、张海博指导全文修改优化。

详细信息

通信作者:
张海博， 15289317954@163.com （ORCID：0000-0003-1755-1813）

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出版历程
- 收稿日期: 2025-09-02
- 录用日期: 2025-12-31
- 出版日期: 2026-06-25

Association between endoplasmic reticulum stress and ferroptosis in metabolic associated fatty liver disease

1.
School of Traditional Chinese Medicine，Shaanxi University of Chinese Medicine，Xianyang，Shaanxi 712046，China
2.
First Ward Area of Hepatology Hospital，The Affiliated Hospital of Shaanxi University of Chinese Medicine，Xianyang，Shaanxi 712000，China
3.
School of Basic Medical Sciences，Shaanxi University of Chinese Medicine，Xianyang，Shaanxi 712046，China

Research funding:

National Natural Science Foundation of China (82174330);

National Natural Science Foundation of China (82405335);

Youth Innovation Team of Shaanxi Provincial Department of Education (25JP049);

"Double Chain Integration"Innovation Team of Shaanxi Provincial Administration of Traditional Chinese Medicine (2022-SLRH-LJ-002);

Major Science and Technology Innovation Special Project of Xianyang City (L2023-ZDKJ-CYJQ-SF-011);

University-level High-level Key Discipline of Traditional Chinese Medicine,Shaanxi University of Chinese Medicine (2024XKZD19);

Innovative Talents for Traditional Chinese Medicine Research of Shaanxi Province (2025-CXRC-19);

Program for the Construction of Scientific and Technological Innovation Talent System,Shaanxi University of Chinese Medicine (2024-KJXX-03)

More Information

Corresponding author: ZHANG Haibo， 15289317954@163.com （ORCID： 0000-0003-1755-1813）

摘要

摘要: 代谢相关脂肪性肝病（MAFLD）是全球高发的慢性肝病，其向代谢相关脂肪性肝炎、肝纤维化进展的机制尚未完全明确，内质网应激（ERS）与铁死亡（Fer）深度参与其病理演进。本文系统综述了ERS的核心调控机制及其在MAFLD中调控肝细胞脂质代谢、炎症反应与细胞凋亡的作用；分析了Fer的核心机制，同时探讨了MAFLD病理微环境中Fer的诱发因素，以及Fer加剧肝细胞死亡、促进肝纤维化进展的作用；阐述了ERS与Fer的串扰是推动MAFLD进展的关键，为MAFLD临床干预提供新的参考与思路。
- 代谢相关脂肪性肝病 /
- 内质网应激 /
- 铁死亡
Abstract: Metabolic associated fatty liver disease （MAFLD） is a highly prevalent chronic liver disease worldwide， and the mechanism underlying its progression to metabolic associated steatohepatitis and liver fibrosis remain unclear. Endoplasmic reticulum stress （ERS） and ferroptosis （Fer） are deeply involved in the pathological evolution of MAFLD. This article systematically reviews the core regulatory mechanisms of ERS and its role in regulating lipid metabolism， inflammation response， and cell apoptosis in MAFLD. It also analyzes the core mechanism of Fer and discusses the predisposing factors for Fer in the pathological microenvironment of MAFLD， as well as the role of Fer in exacerbating hepatocyte death and activating the progression of liver fibrosis. This article proposes that the crosstalk between ERS and Fer is a key driver for the progression of MAFLD， which provides new references and ideas for the clinical intervention of MAFLD.
- Metabolic Dysfunction-Associated Fatty Liver Disease /
- Endoplasmic Reticulum Stress /
- Ferroptosis

HTML全文

注： MAFLD，代谢相关脂肪性肝病；FFA，游离脂肪酸；ROS，活性氧；CDKN1A，细胞周期蛋白依赖性激酶抑制剂1A；EGR1，早期生长反应因子1；PERK，蛋白激酶R样内质网激酶；IRE1α，肌醇需求酶1α；ATF6，激活转录因子6；CHOP，CCAAT增强子结合蛋白同源蛋白；ACSL4，酰基辅酶A合成酶长链家族4；GPX4，谷胱甘肽过氧化物酶4；TGF-β，转化生长因子β；ECM，细胞外基质。

图 1 内质网应激参与铁死亡促进MAFLD

Figure 1. Endoplasmic reticulum stress involvement in ferroptosis promoting MAFLD

下载: 全尺寸图片幻灯片

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