脂多糖在代谢功能障碍相关脂肪性肝病发病机制中的作用*

doi:10.3969/j.issn.1672-5069.2026.02.001

实用肝脏病杂志 ›› 2026, Vol. 29 ›› Issue (2): 161-166.doi: 10.3969/j.issn.1672-5069.2026.02.001

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脂多糖在代谢功能障碍相关脂肪性肝病发病机制中的作用^*

黄锦, 李佳豪, 徐雨轩, 刘小微, 熊思妍, 徐雨鹏, 罗英, 洪芬芳, 杨树龙

344100 江西省抚州市南昌大学抚州医学院生理教研室

收稿日期:2025-08-12 出版日期:2026-03-10 发布日期:2026-03-13
通讯作者: 杨树龙,E-mail:shulongyang@qq.com
作者简介:黄锦,男,22,大学本科。E-mail:a2021060782@163.com;共同第一作者:李佳豪,男,22,大学本科。E-mail:13397916517@163.com
基金资助:
^*国家自然科学基金资助项目(编号:82360880/82060661/81660151);江西省自然科学基金资助项目(编号:20232ACB206057);江西省高等学校教学改革研究项目(编号:JXJG-22-130-1);抚州市社会发展指导性科技计划项目[编号:抚科社字(2022)9号]

Role of lipopolysaccharide in the pathogenesis of metabolic dysfunction-associated steatotic liver disease

Huang Jin, Li Jiahao, Xu Yuxuan, et al

Department of Physiology. Nanchang University Fuzhou Medical College, Fuzhou 344100, Jiangxi Province, China

Received:2025-08-12 Online:2026-03-10 Published:2026-03-13

摘要/Abstract

关键词: 代谢功能障碍相关脂肪性肝病, 脂多糖, 发生机制

Key words: Metabolic dysfunction-associated steatotic liver disease, Lipopolysaccharide, Pathogenesis

黄锦, 李佳豪, 徐雨轩, 刘小微, 熊思妍, 徐雨鹏, 罗英, 洪芬芳, 杨树龙. 脂多糖在代谢功能障碍相关脂肪性肝病发病机制中的作用^*[J]. 实用肝脏病杂志, 2026, 29(2): 161-166.

Huang Jin, Li Jiahao, Xu Yuxuan, et al. Role of lipopolysaccharide in the pathogenesis of metabolic dysfunction-associated steatotic liver disease[J]. Journal of Practical Hepatology, 2026, 29(2): 161-166.

参考文献

[1] Friedman S L, Neuschwander-Tetri B A, Rinella M, et al. Mechanisms of nafld development and therapeutic strategies. Nat Med,2018,24(7):908-922.
[2] 于洋,付晓燕,吴艳红,等. 低剂量LPS通过上调巨噬细胞TLR4表达促进非酒精性脂肪性肝炎进展. 第三军医大学学报,2021,43(22):2423-2434.
[3] 姜慧卿. 非酒精性脂肪性肝病的临床表现与病理学特点. 中国全科医学,2007,(24):2030-2033.
[4] Coutinho-Wolino K S, Almeida P P, Mafra D, et al. Bioactive compounds modulating toll-like 4 receptor (tlr4)-mediated inflammation: Pathways involved and future perspectives. Nutrition Research,2022,107:96-116.
[5] Jang j h, Shin h w, Lee j m, et al. An overview of pathogen recognition receptors for innate immunity in dental pulp. Mediators Inflamm,2015,2015:794143.
[6] Goulopoulou S, Mccarthy C G, Webb R C. Toll-like receptors in the vascular system: Sensing the dangers within. Pharmacol Rev,2016,68(1):142-167.
[7] Takeda K, Akira S. Toll-like receptors in innate immunity. Int Immunol,2005,17(1):1-14.
[8] Anderson KV, Bokla L, Nusslein-Volhard C. Establishment of dorsal-ventral polarity in the drosophila embryo: the induction of polarity by the toll gene product. Cell,1985,42(3):791-798.
[9] Kawai T, Akira S. The roles of tlrs, rlrs and nlrs in pathogen recognition. Int Immunol,2009,21(4):317-337.
[10] Mogensen T H. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev,2009,22(2):240-273.
[11] Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Front Immunol,2014,5:461.
[12] Kumar H, Kawai T, Akira S. Pathogen recognition by the innate immune system. Int Rev Immunol,2011,30(1):16-34.
[13] Zhao X J, Dong Q, Bindas J, et al. Trif and irf-3 binding to the tnf promoter results in macrophage tnf dysregulation and steatosis induced by chronic ethanol. J Immunol,2008,181(5):3049-3056.
[14] Kagan J C, Su T, Horng T, et al. Tram couples endocytosis of toll-like receptor 4 to the induction of interferon-beta. Nat Immunol,2008,9(4):361-368.
[15] Seki E, Brenner D A. Toll-like receptors and adaptor molecules in liver disease: update. Hepatology,2008,48(1):322-335.
[16] Guo J, Friedman S L. Toll-like receptor 4 signaling in liver injury and hepatic fibrogenesis. Fibrogenesis Tissue Repair,2010,3:21.
[17] Alisi A, Carsetti R, Nobili V. Pathogen- or damage-associated molecular patterns during nonalcoholic fatty liver disease development. Hepatology,2011,54(5):1500-1502.
[18] Takeda K, Akira S. Tlr signaling pathways. Semin Immunol,2004,16(1):3-9.
[19] Alisi A, Da Sacco L, Bruscalupi G, et al. Mirnome analysis reveals novel molecular determinants in the pathogenesis of diet-induced nonalcoholic fatty liver disease. Lab Invest,2011,91(2):283-293.
[20] Myokai F, Takashiba S, Lebo R, et al. A novel lipopolysaccharide-induced transcription factor regulating tumor necrosis factor alpha gene expression: molecular cloning, sequencing, characterization, and chromosomal assignment. Proc Natl Acad Sci U S A,1999,96(8):4518-4523.
[21] Tang X, Metzger D, Leeman S, et al. Lps-induced tnf-alpha factor (litaf)-deficient mice express reduced lps-induced cytokine: Evidence for litaf-dependent lps signaling pathways. Proc Natl Acad Sci U S A,2006,103(37):13777-13782.
[22] Soares J B, Pimentel-Nunes P, Roncon-Albuquerque R, et al. The role of lipopolysaccharide/toll-like receptor 4 signaling in chronic liver diseases. Hepatol Int,2010,4(4):659-672.
[23] Rivera C A, Adegboyega P, Van Rooijen N, et al. Toll-like receptor-4 signaling and Kupffer cells play pivotal roles in the pathogenesis of non-alcoholic steatohepatitis. J Hepatol,2007,47(4):571-579.
[24] Schwabe R F, Seki E, Brenner D A. Toll-like receptor signaling in the liver. Gastroenterology,2006,130(6):1886-1900.
[25] Van Bossuyt H, De Zanger R B, Wisse E. Cellular and subcellular distribution of injected lipopolysaccharide in rat liver and its inactivation by bile salts. J Hepatol,1988,7(3):325-337.
[26] Mimura Y, Sakisaka S, Harada M, et al. Role of hepatocytes in direct clearance of lipopolysaccharide in rats. Gastroenterology,1995,109(6):1969-1976.
[27] Harte A L, Da Silva N F, Creely S J, et al. Elevated endotoxin levels in non-alcoholic fatty liver disease. J Inflamm (Lond),2010,7:15.
[28] Mehta N N, Mcgillicuddy F C, Anderson P D, et al. Experimental endotoxemia induces adipose inflammation and insulin resistance in humans. Diabetes,2010,59(1):172-181.
[29] Wu R, Nakatsu G, Zhang X, et al. Pathophysiological mechanisms and therapeutic potentials of macrophages in non-alcoholic steatohepatitis. Expert Opin Ther Targets,2016,20(5):615-626.
[30] Schroder K, Tschopp J. The inflammasomes. Cell,2010,140(6):821-832.
[31] Stienstra R, Van Diepen J A, Tack C J, et al. Inflammasome is a central player in the induction of obesity and insulin resistance. Proc Natl Acad Sci U S A,2011,108(37):15324-15329.
[32] Henao-Mejia J, Elinav E, Jin C, et al. Inflammasome-mediated dysbiosis regulates progression of nafld and obesity. Nature,2012,482(7384):179-185.
[33] kitazawa t, tsujimoto t, kawaratani h, et al. Expression of toll-like receptor 4 in various organs in rats with d-galactosamine-induced acute hepatic failure. J Gastroenterol Hepatol,2008,23(8 Pt 2):e494-e498.
[34] 黄珊,宁佐伟,王国正,等. 脂多糖通过NOD样受体蛋白3炎症小体通路诱导大鼠急性肝损伤实验研究. 陕西医学杂志,2021,50(3):264-267,e71.
[35] Martinon F, Mayor A, Tschopp J. The inflammasomes: guardians of the body. Annu Rev Immunol,2009,27:229-265.
[36] Martinon F, Burns K, Tschopp J. The inflammasome:a molecular platform triggering activation of inflammatory caspases and processing of proIL-β. Mol Cell,2002,10(2):417-426.
[37] Zhu F, Ma J, Li W, et al. The orphan receptor nur77 binds cytoplasmic lps to activate the non-canonical nlrp3 inflammasome. Immunity,2023,56(4):753-767.
[38] Tang T, Lang X, Xu C, et al. Clics-dependent chloride efflux is an essential and proximal upstream event for nlrp3 inflammasome activation. Nat Commun,2017,8(1):202.
[39] Vandanmagsar B, Youm Y H, Ravussin A, et al. The nlrp3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med,2011,17(2):179-188.
[40] Chen X, Liu G, Yuan Y, et al. Nek7 interacts with nlrp3 to modulate the pyroptosis in inflammatory bowel disease via nf-kappab signaling. Cell Death Dis,2019,10(12):906.
[41] Franchi L, Warner N, Viani K, et al. Function of nod-like receptors in microbial recognition and host defense. Immunol Rev,2009,227(1):106-128.
[42] Yang X D, Li W, Zhang S, et al. Plk4 deubiquitination by spata2-cyld suppresses nek7-mediated nlrp3 inflammasome activation at the centrosome. EMBO J,2020,39(2):e102201.
[43] Compare D, Coccoli P, Rocco A, et al. Gut-liver axis: the impact of gut microbiota on non alcoholic fatty liver disease. Nutr Metab Cardiovasc Dis,2012,22(6):471-476.
[44] Miura K, Ishioka M, Iijima K. The roles of the gut microbiota and toll-like receptors in obesity and nonalcoholic fatty liver disease. J Obes Metab Syndr,2017,26(2):86-96.
[45] Guan B, Tong J, Hao H, et al. Bile acid coordinates microbiota homeostasis and systemic immunometabolism in cardiometabolic diseases. Acta Pharm Sin B,2022,12(5):2129-2149.
[46] Vasques-Monteiro I M L, Silva-Veiga F M, Miranda C S, et al. A rise in proteobacteria is an indicator of gut-liver axis-mediated nonalcoholic fatty liver disease in high-fructose-fed adult mice. Nutr Res,2021,91:26-35.
[47] Gangarapu V, Yildiz K, Ince A T, et al. Role of gut microbiota: Obesity and nafld. Turk J Gastroenterol,2014,25(2):133-140.
[48] Shen B, Wang J, Guo Y, et al. Dextran sulfate sodium salt-induced colitis aggravates gut microbiota dysbiosis and liver injury in mice with non-alcoholic steatohepatitis. Front Microbiol,2021,12:756299.

脂多糖在代谢功能障碍相关脂肪性肝病发病机制中的作用^*

Role of lipopolysaccharide in the pathogenesis of metabolic dysfunction-associated steatotic liver disease

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