晚期肝病中肠肝轴的新发现：一个有希望的治疗靶点。

IF 5.6 2区医学 Q1 PHARMACOLOGY & PHARMACY

Biochemical pharmacology Pub Date : 2025-09-03 DOI:10.1016/j.bcp.2025.117284

Yunqi Xing, Yanghao Ou, Yujie Wang, Luming Hou, Junfeng Zhu

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引用次数: 0

摘要

肠-肝轴构成了肠-肝系统之间的双向通讯网络，整合了生态微环境、代谢和免疫信号。目前，有令人信服的证据表明，肠-肝轴的整体功能障碍是晚期肝病发病的关键驱动因素。本文就肠屏障各组成部分在肝硬化及其并发症发生、发展中的作用及其最新研究进展作一综述。长期暴露于多因素应激源可导致肠道物理化学屏障、微生物生态失调和免疫失调的不可逆损伤。这些肠-肝轴内的累积扰动增强了病原微生物的易位，启动了全身炎症反应，并加速了疾病的进展。对肠-肝串扰机制的更深入了解有望为恢复以微生物群为目标的肠道稳态提供新的治疗策略，这可能导致失代偿肝硬化的功能再代偿。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

New insights into gut-liver axis in advanced liver diseases: A promising therapeutic target

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New insights into gut-liver axis in advanced liver diseases: A promising therapeutic target

The gut-liver axis constitutes a bidirectional communication network that integrates the microbial microenvironment, metabolism, and immune signals between the gut and the liver. Currently, there is compelling evidence indicating that the overall dysfunction of the gut-liver axis is a pivotal driver in the pathogenesis of advanced liver diseases. This review focuses on the latest research progress regarding various components of the intestinal barrier and how these components contribute to the onset and progression of cirrhosis and its complications. Chronic exposure to multifactorial stressors can result in irreversible damage to intestinal physical barriers, microbial dysbiosis, and immune dysregulation. These cumulative perturbations within the gut-liver axis promote pathogenic microbial translocation, initiate systemic inflammatory responses, and expedite disease progression. A more in-depth understanding of the gut-liver crosstalk mechanism is anticipated to offer novel therapeutic strategies for restoring microbiota-targeted intestinal homeostasis, which may lead to functional recompensation in decompensated cirrhosis.

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来源期刊

Biochemical pharmacology 医学-药学

CiteScore

10.30

自引率

1.70%

发文量

420

审稿时长

17 days

期刊介绍： Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics. The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process. All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review. While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.