慢加急性肝衰竭能量代谢紊乱的代谢组学特征及相关靶向治疗策略

陈鑫鑫; 罗娟; 叶凤琴; 莫征远; 王秀峰

doi:10.12449/JCH260731

慢加急性肝衰竭能量代谢紊乱的代谢组学特征及相关靶向治疗策略

DOI: 10.12449/JCH260731

1.
广西中医药大学研究生学院，南宁 530222
2.
广西中医药大学第一附属医院肝病一区，南宁 530023

基金项目:

广西壮族自治区自然基金项目 (2023GXNSFAA026380)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：陈鑫鑫、王秀峰对文章的思路及设计有关键贡献；陈鑫鑫负责拟定写作框架并撰写文章；罗娟、叶凤琴、莫征远参与文献检索及论文修订；王秀峰负责指导修改并最终定稿。

详细信息

通信作者:
王秀峰， 52912236@qq.com （ORCID： 0000-0003-0841-5908）

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出版历程
- 收稿日期: 2025-10-30
- 录用日期: 2025-12-09
- 出版日期: 2026-07-25

Metabolomic features of energy metabolic dysregulation and related targeted therapeutic strategies in acute-on-chronic liver failure

1.
Graduate School of Guangxi University of Chinese Medicine，Nanning 530222，China
2.
First Ward of Hepatology，The First Affiliated Hospital of Guangxi University of Chinese Medicine，Nanning 530023，China

Research funding:

Natural Seience Foundation of Guangxi Zhuang Autonomous Region (2023GXNSFAA026380)

More Information

Corresponding author: Wang Xiufeng， 52912236@qq.com （ORCID： 0000-0003-0841-5908）

摘要

摘要: 慢加急性肝衰竭是一种在慢性肝病基础上发生的急性失代偿综合征，以短期高病死率为特征。代谢组学揭示其存在显著能量代谢重编程，表现为糖、脂、氨基酸、线粒体代谢及肠道菌群失调的广泛紊乱状态，并与系统性炎症、免疫失衡密切相关，共同推动病情进展。糖异生抑制及糖酵解亢进、脂肪酸β-氧化受阻、线粒体氧化磷酸化受抑制、氨代谢失衡和肠道菌群失调等构成核心代谢表型。本文整合了近年代谢组学与分子机制研究，系统梳理了五大代谢网络的紊乱特征。针对能量代谢干预，归纳糖代谢调节、脂代谢干预、线粒体靶向保护、肠道菌群再平衡、氨基酸优化等五大策略，并评估其应用价值与未来转化前景，为治疗、缓解甚至逆转疾病进程的思路提供科学依据。
- 慢加急性肝功能衰竭 /
- 能量代谢 /
- 代谢组学
Abstract: Acute-on-chronic liver failure is an acute decompensated syndrome that occurs on the basis of chronic liver disease and is characterized by a high short-term mortality rate. Metabolomics reveals the presence of significant energy metabolic reprogramming， manifesting as extensive dysregulation of glucose/lipid/amino acid metabolism， mitochondrial metabolism， and intestinal flora， and it closely interacts with systemic inflammation and immune imbalance， jointly promoting disease progression. The core metabolic phenotypes include suppressed gluconeogenesis， enhanced glycolysis， impaired β-oxidation， inhibited mitochondrial oxidative phosphorylation， ammonia metabolic imbalance， and gut microbiota dysbiosis. This article analyzes the latest studies on metabolomic and molecular mechanisms and systematically reviews the dysregulation characteristics of the five major metabolic networks. In terms of intervention for energy metabolism， this article summarizes the five strategies of glucose metabolism regulation， lipid metabolism intervention， mitochondria-targeted protection， gut microbiota rebalancing， and amino-acid optimization and assesses their application value and prospects for clinical translation， so as to provide a scientific basis for the treatment， alleviation， and even reversal of disease progression.
- Acute-On-Chronic Liver Failure /
- Energy Metabolism /
- Metabolomics

HTML全文

注： ATP，三磷酸腺苷；ROS，活性氧；OXPHOS，氧化磷酸化；ACLF，慢加急性肝衰竭。

图 1 ACLF代谢组学“五环联动”机制示意图

Figure 1. Schematic illustration of the “five-ring interlocking” mechanism of ACLF metabolomics

下载: 全尺寸图片幻灯片

注： GLUT1，葡萄糖转运蛋白1；HK，己糖激酶；PFKFB3，6-磷酸果糖激酶-2/果糖-2，6-二磷酸酶3；ROS，活性氧；ACLF，慢加急性肝衰竭。

图 2 ACLF炎症环境下细胞内代谢重编程介导多器官功能衰竭的分子机制及干预靶点示意图

Figure 2. Schematic diagram of the molecular mechanisms and therapeutic targets of multi-organ failure mediated by intracellular metabolic reprogramming under the inflammatory environment of ACLF

下载: 全尺寸图片幻灯片

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