线粒体DNA释放触发的先天免疫机制在代谢相关脂肪性肝病中的作用及靶向干预策略

周禹; 李开楊; 杨梅; 赵琦; 赵一鸣; 张飞; 汪倩

doi:10.12449/JCH260832

线粒体DNA释放触发的先天免疫机制在代谢相关脂肪性肝病中的作用及靶向干预策略

DOI: 10.12449/JCH260832

周禹¹,
李开楊¹,
杨梅^2, , ,,
赵琦³,
赵一鸣¹,
张飞¹,
汪倩¹

1.
贵州中医药大学第二临床医学院，贵阳 550002
2.
贵州中医药大学第二附属医院检验科，贵阳 550001
3.
贵州中医药大学第二附属医院消化内科，贵阳 550001

基金项目:

国家自然科学基金 (82160866);

贵州省科技计划项目 (Qiankehe Jichu-ZK［2023］General 433);

贵州省中医药、民族医药科学技术研究课题 (QZYY-2025-182)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：周禹负责选题及撰写论文；李开楊负责拟定思路；杨梅负责审核及定稿；赵琦负责指导撰写文章；赵一鸣、张飞和汪倩负责查找文献及修改论文。

详细信息

通信作者:
杨梅， 908417289@qq.com （ORCID： 0009-0003-3563-4767）

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出版历程
- 收稿日期: 2025-12-22
- 录用日期: 2026-01-12
- 出版日期: 2026-08-25

Role of innate immune mechanisms triggered by mitochondrial DNA release in metabolic dysfunction-associated fatty liver disease and targeted intervention strategies

1.
The Second Clinical Medical School of Guizhou University of Traditional Chinese Medicine，Guiyang 550002，China
2.
Department of Clinical Laboratory，The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine，Guiyang 550001，China
3.
Department of Gastroenterology，The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine，Guiyang 550001，China

Research funding:

National Natural Science Foundation of China (82160866);

Science and Technology Planning Project of Guizhou Province (Qiankehe Jichu-ZK［2023］General 433);

Traditional Chinese Medicine and Ethnic Medicine Science and Technology Research Project of Guizhou Province (QZYY-2025-182)

More Information

Corresponding author: Yang Mei， 908417289@qq.com （ORCID： 0009-0003-3563-4767）

摘要

摘要: 代谢相关脂肪性肝病（MAFLD）是全球发病率最高的慢性肝病，其发病机制复杂。线粒体在该疾病进程中发挥关键作用，研究证实线粒体功能障碍可加剧代谢紊乱、诱发先天免疫失衡，而线粒体DNA（mtDNA）是介导这两大病理效应的核心分子。mtDNA异常释放后，可被细胞内模式识别受体识别，进而触发先天免疫反应并引发组织损伤，形成“mtDNA释放-免疫激活-组织损伤”的病理通路。目前，该通路在MAFLD疾病不同阶段的作用机制以及靶向该通路的干预策略，尚缺乏系统性的综述总结。本文系统综述该通路的核心分子机制、在MAFLD发生发展中的病理作用及当前靶向该机制的干预策略，旨在为MAFLD的病理机制解析与新型治疗策略的开发提供理论依据。
- 代谢相关脂肪性肝病 /
- DNA，线粒体 /
- 免疫，先天 /
- 信号传导
Abstract: Metabolic dysfunction-associated fatty liver disease （MAFLD） is the most prevalent chronic liver disease worldwide， with a complex pathogenesis. Mitochondria play a pivotal role in this disease process， and studies have confirmed that mitochondrial dysfunction can exacerbate metabolic disorders and induce innate immune imbalance， while mitochondrial DNA （mtDNA） is the core molecule mediating these two pathological effects. After the abnormal release of mtDNA， it can be recognized by intracellular pattern recognition receptors， which in turn triggers innate immune responses and causes tissue damage， forming a pathological pathway of “mtDNA release-immune activation-tissue damage”. Currently， there is a lack of systematic reviews summarizing the mechanism of action of this pathway in different stages of MAFLD and the intervention strategies targeting this pathway. This article systematically reviews the core molecular mechanism of this pathway， its pathological role in the development and progression of MAFLD， and the current intervention strategies targeting this mechanism， in order to provide a theoretical basis for analyzing the pathogenesis of MAFLD and developing novel therapeutic strategies.
- Metabolic Dysfunction-Associated Fatty Liver Disease /
- DNA， Mitochondrial /
- Immunity， Innate /
- Signal Transduction

HTML全文

注： cGAS，环鸟苷酸-腺苷酸合酶；cGAMP，环鸟苷酸-腺苷酸；STING，干扰素基因刺激因子；TBK1，TANK结合激酶1；IRF3，干扰素调节因子3；IKK，IκB激酶；TNF-α，肿瘤坏死因子α；IL-6，白细胞介素6；NLRP3，核苷酸结合寡聚结构域样受体家族热蛋白结构域相关蛋白3；Caspase-1，胱天蛋白酶1；IL-1β，白细胞介素1β；IL-18，白细胞介素18；TLR9，Toll样受体9；MyD88，髓系分化初级反应蛋白质88；NF-κB，核因子κB。

图 1 线粒体DNA触发先天免疫机制的信号通路

Figure 1. Signal pathway of innate immune mechanisms triggered by mitochondrial DNA

下载: 全尺寸图片幻灯片

注： mtDNA，线粒体DNA；JNK/IKK，c-Jun氨基端激酶/IκB激酶；IRS，胰岛素受体底物；NF-κB，核因子κB；SREBP-1c，固醇调节元件结合蛋白1c；ROS，活性氧；TNF-α，肿瘤坏死因子α；IL-6，白细胞介素6。

图 2 线粒体DNA-先天免疫通路参与的恶性循环

Figure 2. The vicious cycle mediated by the mitochondrial DNA-innate immunity pathway

下载: 全尺寸图片幻灯片

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