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线粒体功能障碍与细胞间通讯在代谢相关脂肪性肝炎中的作用机制
DOI: 10.12449/JCH260833
利益冲突声明：本文不存在任何利益冲突。
作者贡献声明：罗婉艺负责撰写论文；张津铭负责修改论文；罗婉艺、曾国城和马骁天负责归纳文献；于牧鑫和郑楚伟负责拟定写作思路；季霞和张津铭负责指导撰写文章并最后定稿。
Mechanism of action of mitochondrial dysfunction and intercellular communication in metabolic dysfunction-associated steatohepatitis
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摘要: 代谢相关脂肪性肝病（MAFLD）在脂质毒性、炎症浸润等因素作用下，肝细胞线粒体稳态失衡并出现功能障碍，进而进展为代谢相关脂肪性肝炎（MASH）。近年研究证实，线粒体损伤与慢性炎症密切相关，而细胞外囊泡是连接二者的核心媒介。本文系统综述了MAFLD/MASH中肝细胞线粒体损伤的分子机制，重点阐明肝细胞来源细胞外囊泡对肝内炎症的调控作用，并探讨线粒体靶向治疗及细胞间通讯干预在MAFLD/MASH中的潜在应用前景，旨在为开发此类疾病的新型治疗策略提供理论依据。Abstract: Metabolic dysfunction-associated fatty liver disease （MAFLD） progresses to metabolic dysfunction-associated steatohepatitis （MASH） due to mitochondrial homeostasis imbalance and dysfunction in hepatocytes caused by various factors such as lipotoxicity and inflammatory infiltration. Recent studies have confirmed that mitochondrial injury is closely associated with chronic inflammation， with extracellular vesicle （EV） acting as a key mediator linking the two processes. This article systematically reviews the molecular mechanisms of hepatocyte mitochondrial dysfunction in MAFLD/MASH， highlights the regulatory role of hepatocyte-derived EV in intrahepatic inflammation， and discusses the potential application prospects of mitochondria-targeted therapies and intercellular communication interventions in MAFLD/MASH， in order to provide a theoretical basis for developing novel therapeutic strategies for these diseases.
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注： EV，细胞外囊泡；mtDNA，线粒体DNA；miR，微RNA；ER，内质网；RBP4，视黄醇结合蛋白4；TGM2，转谷氨酰胺酶2；TLR9，Toll样受体9；Rictor，雷帕霉素不敏感伴侣蛋白；Akt，蛋白激酶B；FoxO1，叉头框蛋白O1；NOX2，还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶2；ROS，活性氧；NF-κB，核因子κB；IL，白细胞介素；TNF-α，肿瘤坏死因子α；M1，巨噬细胞M1型（促炎型）；WASL，威斯科特-奥尔德里奇综合征蛋白样肌动蛋白成核促进因子；NET，中性粒细胞胞外陷阱；HCC，肝细胞癌；LIMA1，LIM结构域与肌动蛋白结合蛋白1；MASP1，甘露聚糖结合凝集素相关丝氨酸蛋白酶1；ACTA2，α-平滑肌肌动蛋白2；Fibronectin，纤维连接蛋白；Timp1，金属蛋白酶组织抑制剂1；p38 MAPK，p38丝裂原活化蛋白激酶；ATF2，活化转录因子2；Nr1d2，核受体亚家族1D组成员2；Smad7，母系抗十五表态蛋白同源物7；MASH，代谢相关脂肪性肝炎。
图 1 肝细胞来源EV在MASH慢性炎症网络中的调控作用
Figure 1. Regulation of hepatocyte-derived extracellular vesicle in the chronic inflammatory network of MASH
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