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乳酸化修饰在慢性肝病中的调控作用机制
DOI: 10.12449/JCH251232
利益冲突声明：本文不存在任何利益冲突。
作者贡献声明：容碧晴负责课题设计，资料分析，撰写论文；王佳慧、汪磊、罗淑娟、万宛若、杨仕权参与收集数据，修改论文；郑洋、张荣武、肖华业负责拟定写作思路，指导撰写文章并最后定稿。
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摘要: 慢性肝病是指肝脏长期受各种致病因素的影响，逐渐发展为肝炎、肝纤维化、肝硬化甚至肝癌的病理过程，是一类严重影响肝脏功能的复杂难治性疾病。作为一种新型的蛋白质翻译后修饰，乳酸化修饰通过将乳酸共价连接至靶蛋白的赖氨酸残基，从而动态地调控基因的转录表达与下游细胞功能。近年研究发现，慢性肝病常伴随乳酸代谢异常。乳酸作为肝脏代谢的关键产物，其研究价值日益凸显；而乳酸化修饰则以代谢-表观遗传交互为中介，在肝病的代谢重编程、免疫调控及纤维化进程中发挥着关键作用。本文在概述慢性肝病流行病学的基础上，重点综述了乳酸化修饰的分子机制，其对肝细胞代谢、基因通路及肝星状细胞活化的调控作用，并探讨其作为诊断标志物和治疗靶点的潜力，旨在为揭示乳酸化修饰在慢性肝病的生物化学与分子生物学中的作用机制提供新思路。Abstract: Chronic liver disease refers to the pathological process in which the liver is affected by various pathogenic factors for a long time， gradually leading to hepatitis， hepatic fibrosis， liver cirrhosis， and even hepatocellular carcinoma， and it is a group of complex refractory diseases that severely impairs liver function. As a novel post-translational and epigenetic modification， lactylation modification dynamically regulates gene transcriptional expression and downstream cellular function through the covalent binding of lactate to lysine residues on target proteins. Recent studies have shown that chronic liver disease is often accompanied by abnormal lactate metabolism. As a key metabolic product of the liver， lactate holds a significant research value， and lactylation modification plays a pivotal role in metabolic reprogramming， immune regulation， and fibrogenesis through metabolic-epigenetic interactions. This article introduces the epidemiology of chronic liver disease and reviews the molecular mechanism of lactylation modification and its regulatory effect on hepatocyte metabolism， gene pathways， and hepatic stellate cell activation， as well as its potential as a diagnostic biomarker and a therapeutic target， in order to provide new insights into the biochemical and molecular biological mechanisms of lactylation modification in chronic liver disease.
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Key words:
- Lactylation Modification /
- Chronic Liver Disease /
- Proteomics
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注： LDHA，乳酸脱氢酶A；MCT1，单羧酸转运体1；TCA循环，三羧酸循环。
图 1 乳酸代谢及乳酸化修饰机制图
Figure 1. Lactic acid metabolism and Lactylation modification mechanism diagram
注： LLPS，液-液相分离；H3K18，组蛋白H3第18位赖氨酸；HSC，肝星状细胞；ECM，细胞外基质；LDHA，乳酸脱氢酶A；HK2，己糖激酶-2；α-SMA，α-平滑肌肌动蛋白。
图 2 乳酸化修饰调控肝纤维化
Figure 2. Lactylation modification regulates Hepatic fibrosis
注： H3K18，组蛋白H3第18位赖氨酸；HTG，中药复方化浊调脂颗粒；SREBP1c，固醇调节元件结合蛋白1c；FASN，脂肪酸合酶；ACC1，乙酰辅酶A羧化酶1；NAFLD，非酒精性脂肪性肝病；FFA，游离脂肪酸。
图 3 乳酸化修饰调控NAFLD
Figure 3. Lactylation modification regulates NAFLD
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