组蛋白乳酸化修饰在肝纤维化中的调控作用

曾唯楚; 吕星; 李丰帆; 刘珍妮; 李俊钢; 张伟林; 刘佩婷; 李炳杵; 陈若虹; 陈芷阳; 胡敏

doi:10.12449/JCH260328

组蛋白乳酸化修饰在肝纤维化中的调控作用

DOI: 10.12449/JCH260328

中南大学湘雅二医院检验医学科，湖南省临床分子诊断中心，分子诊断技术湖南省工程研究中心，湖南省感染性疾病分子诊断临床医学研究中心，长沙 410011

基金项目:

国家自然科学基金 (82270658);

中南大学研究生创新项目 (2024XQLH103)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：曾唯楚、胡敏负责设计综述框架，起草综述；曾唯楚负责绘制图表；曾唯楚、胡敏、陈芷阳、吕星、李丰帆负责综述修改；曾唯楚、吕星、李丰帆、刘珍妮、李俊钢、张伟林、刘佩婷、李炳杵、陈若虹、陈芷阳、胡敏负责拟定综述思路，指导撰写文章并最后定稿。

详细信息

通信作者:
胡敏， huminjyk@csu.edu.cn （ORCID： 0000-0001-7886-8174）

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出版历程
- 收稿日期: 2025-07-15
- 录用日期: 2025-08-06
- 出版日期: 2026-03-25

Regulatory effect of histone lactylation modification in hepatic fibrosis

Department of Laboratory Medicine，The Second Xiangya Hospital of Central South University，Hunan Clinical Molecular Diagnosis Center，Hunan Engineering Research Center of Molecular Diagnosis Technology，Hunan Clinical Medical Research Center of Molecular Diagnosis of Infectious Diseases，Changsha 410011，China

Research funding:

National Natural Science Foundation of China (82270658);

Postgraduate Innovation Project of Central South University (2024XQLH103)

More Information

Corresponding author: HU Min， huminjyk@csu.edu.cn （ORCID： 0000-0001-7886-8174）

摘要

摘要: 肝纤维化是多种慢性肝病共有的可逆性病理过程，与肝硬化和肝癌等严重肝脏疾病的发生发展密切相关，已成为全球范围内的重大健康问题之一。近年来，新发现的表观遗传修饰组蛋白乳酸化被证实参与调控肝纤维化进程。本文系统综述了组蛋白乳酸化在炎症微环境与肝纤维化相互作用中的核心调控作用，旨在阐明“炎症-肝纤维化”级联调控机制，为肝纤维化的早期诊断、靶向干预及阻断恶性转化提供新视角。
- 组蛋白乳酸化 /
- 肝纤维化 /
- 肝星状细胞
Abstract: Hepatic fibrosis is a reversible pathological process in various chronic liver diseases and is closely associated with the development and progression of severe liver diseases such as liver cirrhosis and hepatocellular carcinoma， and it has emerged as a significant global health challenge. In recent years， studies have shown that histone lactylation， a newly discovered epigenetic modification， actively participates in regulating the progression of hepatic fibrosis. This article systematically reviews the core regulatory effect of histone lactylation modification in the interaction between inflammatory microenvironment and hepatic fibrosis， in order to clarify the cascade regulatory mechanism of “inflammation-hepatic fibrosis” and provide new insights for early diagnosis， targeted intervention， and prevention of malignant transformation in hepatic fibrosis.
- Histone Lactylation /
- Hepatic Fibrosis /
- Hepatic Stellate Cells

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注： a，肝星状细胞的代谢重编程驱动组蛋白乳酸化修饰；b，组蛋白乳酸化修饰的表观遗传调控结果。HSC，肝星状细胞；Smad，母系抗十五表态蛋白同源物；TGF-β，转化生长因子β；TNF-α，肿瘤坏死因子α；IL-6，白细胞介素6；α-SMA，α-平滑肌肌动蛋白；COL1A1，Ⅰ型胶原α1；TIMP1，基质金属蛋白酶抑制剂1；HK2，己糖激酶2；LDH，乳酸脱氢酶。

图 1 组蛋白乳酸化修饰调控肝纤维化进程的模式图

Figure 1. Schematic diagram of histone lactylation modification regulating hepatic fibrosis progression

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表 1 靶向组蛋白乳酸化抗肝纤维化策略

Table 1. Targeting histone lactylation： Therapeutic strategies against hepatic fibrosis

靶点	干预手段	模型体系	效应	文献依据
HK2	条件性敲除HK2	肝纤维化小鼠模型	乳酸水平↓、H3K18la↓、α-SMA/COL1A1↓	［29］
LDHA/LDHB	siRNA敲低+shRNA腺病毒抑制	人LX-2细胞/小鼠模型	H3K18la↓、HSC迁移/增殖↓、糖酵解↓	［29，31］
IGF2BP2	CRISPR-Cas9敲除	HSC细胞系	ALDOA↓、乳酸生成↓、HSC活化标志物↓	［30］
乳酸化竞争	HDAC抑制剂（Apicidin/ MS275）	活化HSC	乙酰化↑、乳酸化↓、纤维化基因表达↓	［10］
乳酰辅酶A合成	ACSS2抑制剂（如靶向化合物）	体外HSC模型（待验证）	理论：阻断乳酸化底物供应	［8］（机制推测）
MCT1转运体	AZD3965（MCT1抑制剂）	巨噬细胞-HSC共培养	核内乳酸↓、H3K18la↓、TGF-β释放↓ （预测）	［27］（跨研究引申）
注：HK2，己糖激酶2；H3K18la，组蛋白H3第18位赖氨酸乳酸化；α-SMA，α-平滑肌肌动蛋白；COL1A1，Ⅰ型胶原α1；LDHA/LDHB，乳酸脱氢酶A/乳酸脱氢酶B；IGF2BP2，胰岛素样生长因子2 mRNA结合蛋白2；ALDOA，醛缩酶A；HSC，肝星状细胞；HDAC，组蛋白脱乙酰酶；ACSS2，乙酰辅酶A合成酶2；MCT1，单羧酸转运蛋白1；TGF-β，转化生长因子β。↑表示上调，↓表示下调。

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