[1]赵书菡,王婉瑩,赫俊杰,等.胆汁酸类代谢物在肝脏损伤与治疗中的作用及机制研究进展[J].陕西医学杂志,2025,54(6):856-861.[doi:DOI:10.3969/j.issn.1000-7377.2025.06.026]
　ZHAO Shuhan,WANG Wanying,HE Junjie,et al.Research progress on role and mechanism of bile acid metabolites in liver injury and treatment[J].,2025,54(6):856-861.[doi:DOI:10.3969/j.issn.1000-7377.2025.06.026]
点击复制

胆汁酸类代谢物在肝脏损伤与治疗中的作用及机制研究进展

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
54
期数:
2025年6期
页码:
856-861
栏目:
综 述
出版日期:
2025-06-05

文章信息/Info

Title:
Research progress on role and mechanism of bile acid metabolites in liver injury and treatment
作者:
赵书菡1; 王婉瑩2; 赫俊杰3; 申佰轩2; 黄焱旭2; 刘传鑫2
（1.无锡市新吴区新瑞医院药学部，江苏 无锡 214000；2.河南科技大学临床医学院 河南科技大学第一附属医院内分泌代谢中心，河南 洛阳 471003；3.天津中医药大学中药学院，天津 301617）
Author(s):
ZHAO Shuhan1; WANG Wanying2; HE Junjie3; SHEN Baixuan2; HUANG Yanxu2; LIU Chuanxin2
(1.Department of Pharmacy,Xinrui Hospital,Xinwu District,Wuxi 214000,China;2.Department of Endocrinology and Metabolism,Clinical Medical College,Henan University of Science and Technology,Luoyang 471003,China;3.College of Traditional Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China)
关键词:
胆汁酸; 胆汁酸类代谢物; 肝脏损伤; 牛磺胆酸; 脱氧胆酸; 体质毒理学
Keywords:
Bile acid; Bile acid metabolites; Liver injury; Taurocholic acid; Deoxycholic acid; Constitution-based toxicology
分类号:
R 575
DOI:
DOI:10.3969/j.issn.1000-7377.2025.06.026
文献标志码:
A
摘要:
胆汁酸（BAs）作为重要的代谢与免疫信号分子，在肝脏生理过程中具有双向作用，既能维持肝脏的健康稳态，又能在特定情况下诱发肝脏损伤。BAs类代谢物引发的肝脏损伤过程多由炎症反应、内质网应激、细胞凋亡与坏死以及氧化应激等复杂效应介导。部分BAs通过调节多条信号通路和多种蛋白表达维持BAs系统的代谢运转与循环稳态，从而改善肝脏状况。本文探讨BAs与生物合成代谢间的关系，系统阐述肝脏损伤不同分类，并分析BAs类代谢物诱发肝脏损伤的机制，梳理结合性胆汁酸的治疗作用及机制。
Abstract:
Bile acids (BAs),as an important metabolic and immune signaling molecules,have bidirectional effects in the physiological process of the liver,which can not only maintain the health and homeostasis of the liver,but also induce liver damage under c specific conditions.The process of liver injury triggered by bile acid metabolites is often mediated by complex effects such as inflammatory responses,endoplasmic reticulum stress,cell apoptosis and necrosis,and oxidative stress.Some bile acids maintain the metabolic operation and circulatory homeostasis of the bile acid system by regulating multiple signaling pathways and various protein expressions,thereby improving liver conditions.This article explores the relationship between bile acids and biosynthetic metabolism,systematically elaborates on the different classifications of liver injury,and analyzes the mechanisms by which various bile acid metabolites induce liver injury,as well as the therapeutic mechanisms of conjugated bile acids.

参考文献/References:

[1]JIA W,LI Y,CHEUNG K C P,et al.Bile acid signaling in the regulation of whole body metabolic and immunological homeostasis[J].Sci China Life Sci,2024,67(5)：865-878.
[2]JIA W,XIE G,JIA W.Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis[J].Nat Rev Gastro Hepat,2018,15(2)：111-128.
[3]GUZIOR D V,QUINN R A.Microbial transformations of human bile acids[J].Microbiome,2021,9(1)：140.
[4]DE AGUIAR VALLIM T Q,TARLING E J,EDWARDS P A.Pleiotropic roles of bile acids in metabolism[J].Cell Metab,2013,17(5)：657-669.
[5]STALEY C,WEINGARDEN A R,KHORUTS A,et al.Interaction of gut microbiota with bile acid metabolism and its influence on disease states[J].Appl Microbiol Biot,2017,101：47-64.
[6]KUANG J,WANG J,LI Y,et al.Hyodeoxycholic acid alleviates non-alcoholic fatty liver disease through modulating the gut-liver axis[J].Cell Metab,2023,35(10)：1752-1766.e8.
[7]LEI Y,TANG L,CHEN Q,et al.Disulfiram ameliorates nonalcoholic steatohepatitis by modulating the gut microbiota and bile acid metabolism[J].Nat Commun,2022,13(1)：6862.
[8]CRABB D W,IM G Y,SZABO G,et al.Diagnosis and treatment of alcohol-associated liver diseases：2019 practice guidance from the American Association for the Study of Liver Diseases[J].Hepatology,2020,71(1)：306-333.
[9]LIU Y,LIU T,ZHAO X,et al.New insights into the bile acid-based regulatory mechanisms and therapeutic perspectives in alcohol-related liver disease[J].Cell Mol Life Sci，2022,79(9)：486.
[10]HUANG M,KONG B,ZHANG M,et al.Enhanced alcoholic liver disease in mice with intestine-specific farnesoid X receptor deficiency[J].Lab Invest,2020,100(9)：1158-1168.
[11]王子明,王华.外泌体在肝脏损伤中的研究进展[J].中国药理学通报,2022,38(2)：161-164.
[12]王舒,林森,杨韵秋,等.一贯煎联合多烯磷脂酰胆碱治疗抗结核药物所致肝损伤疗效研究[J].陕西中医,2020,41(3)：328-330.
[13]XIAO X H,ZHAO X,BAI Z F,et al.New outlook on safety of traditional Chinese medicine：Concept and practice[J].China J Chin Mater Med,2023,48(10)：2557-2564.
[14]曾胜澜,梁健芬,邢俊娥,等.铁死亡在药物性肝损伤中的作用机制及治疗研究进展[J].陕西医学杂志,2024,53(12)：1718-1720,1725.
[15]BIAGIOLI M,MARCHIANS,DI GIORGIO C,et al.Combinatorial targeting of G-protein-coupled bile acid receptor 1 and cysteinyl leukotriene receptor 1 reveals a mechanistic role for bile acids and leukotrienes in drug-induced liver injury[J].Hepatology,2023,78(1)：26-44.
[16]LOW E X S,ZHENG Q,CHAN E,et al.Drug induced liver injury：East versus west-a systematic review and meta-analysis[J].Clin Mol Hepatol,2020,26(2)：142.
[17]ROMN-SAGILLO S,QUIONES CASTRO R,JUREZ-FERNNDEZ M,et al.Idiosyncratic drug-induced liver injury and amoxicillin-clavulanate：Spotlight on gut microbiota,fecal metabolome and bile acid profile in patients[J].Int J Mol Sci,2024,25(13)：6863.
[18]刘传鑫,孔娇.体质毒理学：中药安全性评价的新方向[J].世界科学技术-中医药现代化,2023,25(12)：3776-3784.
[19]HOU Z,CHEN L,FANG P,et al.Mechanisms of triptolide-induced hepatotoxicity and protective effect of combined use of isoliquiritigenin：Possible roles of Nrf2 and hepatic transporters[J].Front Pharmacol,2018,9：226.
[20]WEI J,CHEN J,FU L,et al.Polygonum multiflorum thunb suppress bile acid synthesis by activating Fxr-Fgf15 signaling in the intestine[J].J Ethnopharmacol，2019,235：472-480.
[21]JIN D,HUANG N N,WEI J X.Hepatotoxic mechanism of cantharidin：Insights and strategies for therapeutic intervention[J].Front Pharmacol,2023,14：1201404.
[22]BEAUDOIN J J,CLEMENS L,MIEDEL M T,et al.The combination of a human biomimetic liver microphysiology system with BIOLOGXsym,a quantitative systems toxicology (QST) modeling platform for macromolecules,provides mechanistic understanding of tocilizumab-and GGF2-induced liver injury[J].Int J Mol Sci,2023,24(11)：9692.
[23]YANG J,TANG X,LIANG Z,et al.Taurocholic acid promotes hepatic stellate cell activation via S1PR2/p38 MAPK/YAP signaling under cholestatic conditions[J].Clin Mol Hepatol,2023,29(2)：465.
[24]MANCINELLI R,CECI L,KENNEDY L,et al.The effects of taurocholic acid on biliary damage and liver fibrosis are mediated by calcitonin-gene-related peptide signaling[J].Cells,2022,11(9)：1591.
[25]LIU S,GAO Z,HE W,et al.The gut microbiota metabolite glycochenodeoxycholate activates TFR-ACSL4-mediated ferroptosis to promote the development of environmental toxin-linked MAFLD[J].Free Radical Bio Med,2022,193：213-226.
[26]WANG C,YANG M,ZHAO J,et al.Bile salt (glycochenodeoxycholate acid) induces cell survival and chemoresistance in hepatocellular carcinoma[J].J Cell Physiol,2019,234(7)：10899-10906.
[27]GAO L,LV G,LI R,et al.Glycochenodeoxycholate promotes hepatocellular carcinoma invasion and migration by AMPK/mTOR dependent autophagy activation[J].Cancer Lett,2019,454：215-223.
[28]WEI S,MA X,ZHAO Y.Mechanism of hydrophobic bile acid-induced hepatocyte injury and drug discovery[J].Front Pharmacol,2020,11：1084.
[29]XU G,DAI M,ZHENG X,et al.Cholestatic models induced by lithocholic acid and αnaphthylisothiocyanate：Different etiological mechanisms for liver injury but shared JNK/STAT3 signaling[J].Mol Med Rep,2020,22(2)：1583-1593.
[30]LIU T,YANG H,FAN W,et al.Mechanisms of MAFG dysregulation in cholestatic liver injury and development of liver cancer[J].Gastroenterology,2018,155(2)：557-571.e14.
[31]王金枝,孙芳,汪余勤,等.脱氧胆酸诱导氧化应激相关性线粒体去极化对脂肪变性肝细胞损伤的研究[J].临床和实验医学杂志,2019,18(7)：673-676.
[32]YAN T,YAN N,WANG H,et al.FXR-deoxycholic acid-TNF-α axis modulates acetaminophen-induced hepatotoxicity[J].Toxicol Sci,2021,181(2)：273-284.
[33]ANDERMATTEN R B,CIRIACI N,SCHUCK V S,et al.Sphingosine 1-phosphate receptor 2/adenylyl cyclase/protein kinase A pathway is involved in taurolithocholate-induced internalization of Abcc2 in rats[J].Arch Toxicol,2019,93(8)：2279-2294.
[34]AMONYINGCHAROEN S,SURIYO T,THIANTANAWAT A,et al.Taurolithocholic acid promotes intrahepatic cholangiocarcinoma cell growth via muscarinic acetylcholine receptor and EGFR/ERK1/2 signaling pathway[J].Int J Oncol,2015,46(6)：2317-2326.
[35]SONG G,WENG F,ZOU B,et al.Potential therapeutic action of tauroursodeoxycholic acid against cholestatic liver injury via hepatic Fxr/Nrf2 and CHOP-DR5-caspase-8 pathway[J].Clin Sci,2023,137(7)：561-577.
[36]HOU Y,YANG H,CUI Z,et al.Tauroursodeoxycholic acid attenuates endoplasmic reticulum stress and protects the liver from chronic intermittent hypoxia induced injury[J].Exp Ther Med,2017,14(3)：2461-2468.
[37]QI Y,SHI L,DUAN G,et al.Taurochenodeoxycholic acid increases cAMP content via specially interacting with bile acid receptor TGR5[J].Molecules,2021,26(23)：7066.
[38]XU F,WANG J,WANG P,et al.Ursodesoxycholic acid is an FFA4 agonist and reduces hepatic steatosis via FFA4 signaling[J].Eur J Pharmacol,2022,917：174760.
[39]王新伟,杨道坤,梁海军,等.熊去氧胆酸对慢性乙型肝炎患者NAs抗病毒治疗后肝功能异常修复的临床研究[J].陕西医学杂志,2020,49(1)：112-114.
[40]ZHONG J,HE X,GAO X,et al.Hyodeoxycholic acid ameliorates nonalcoholic fatty liver disease by inhibiting RAN-mediated PPARα nucleus-cytoplasm shuttling[J].Nat Commun,2023,14(1)：5451.

备注/Memo

备注/Memo:
国家自然科学基金资助项目(82204938)；河南省医学科技攻关计划项目（LHGJ20240427）
更新日期/Last Update: 2025-06-04