内源性脂质介质在肝衰竭中的应用及潜在价值

颜耿杰; 林镛; 苏会吉; 陈含笑; 班少群; 韦艾凌; 毛德文; 龙富立

doi:10.3969/j.issn.1001-5256.2023.01.033

内源性脂质介质在肝衰竭中的应用及潜在价值

DOI: 10.3969/j.issn.1001-5256.2023.01.033

颜耿杰¹,
林镛¹,
苏会吉¹,
陈含笑¹,
班少群¹,
韦艾凌^{1, 2},
毛德文²,
龙富立^2, , ,

1.
广西中医药大学研究生院，南宁 530200
2.
广西中医药大学第一附属医院肝病二区，南宁 530023

基金项目:

国家自然科学基金课题 (81960841);

国家科技重大专项 (2018ZX10725505-001-011);

广西科技计划项目 (2020GXNSFAA297098);

广西中医药大学校级硕士研究生创新项目 (YCXJ2021034)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：颜耿杰负责课题设计，资料分析，撰写论文；林镛、苏会吉、陈含笑、班少群、龙富立参与收集数据，修改论文；韦艾凌、毛德文、龙富立负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
龙富立，longfuli005@163.com (ORCID: 0000-0003-1196-2697)

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- 被引次数: 0
出版历程
- 收稿日期: 2022-05-11
- 录用日期: 2022-06-16
- 出版日期: 2023-01-20

Application and potential value of endogenous lipid mediators in liver failure

1.
Graduate School of Guangxi University of Chinese Medicine, Nanning 530200, China
2.
Second Ward of Hepatology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China

Research funding:

National Natural Science Foundation of China (81960841);

National Science and Technology Major Project (2018ZX10725505-001-011);

Guangxi Science and technology project (2020GXNSFAA297098);

Guangxi University of Traditional Chinese Medicine Graduate Innovation project (YCXJ2021034)

More Information

Corresponding author: LONG Fuli, longfuli005@163.com (ORCID: 0000-0003-1196-2697)

摘要

摘要: 肝衰竭是临床上常见的终末期肝病症候群，其特征是肝细胞大量坏死导致肝功能迅速衰竭，目前认为其核心机制是过度炎症和免疫反应等。内源性脂质介质参与了多种炎症过程的调节，包括启动、维持和消退，其中类二十烷酸和促分解脂质介质及其复杂的代谢途径和传导信号在这些过程的调节中起关键作用。本文综述了内源性脂质介质在肝衰竭炎症及免疫功能障碍病理生理机制中的关键作用，以及通过脂质免疫途径在肝衰竭中的潜在意义和治疗的新机会，以期为肝衰竭的临床诊疗提供新思路。
- 肝功能衰竭, 急性 /
- 炎症 /
- 免疫
Abstract: Liver failure is a common end-stage liver disease syndrome in clinical practice characterized by massive necrosis of hepatocytes leading to rapid liver failure, and it is currently believed that excessive inflammation and immune response are the core mechanisms of this disease. Endogenous lipid mediators are involved in the regulation of a variety of inflammatory processes, including initiation, maintenance, and regression, and eicosanoids and pro-decomposition lipid mediators, as well as their complex metabolic pathways and transduction signals, play a key role in the regulation of these processes. This article reviews the key role of endogenous lipid mediators in the pathophysiological mechanism of inflammation and immune dysfunction in liver failure and the potential significance and new therapeutic opportunities of lipid immune pathway in liver failure, in order to provide new ideas for the clinical diagnosis and treatment of liver failure.
- Liver Failure, Acute /
- Inflammation /
- Immunity

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参考文献(47)

[1]	LEVY BD, CLISH CB, SCHMIDT B, et al. Lipid mediator class switching during acute inflammation: signals in resolution[J]. Nat Immunol, 2001, 2(7): 612-619. DOI: 10.1038/89759.
[2]	von MOLTKE J, TRINIDAD NJ, MOAYERI M, et al. Rapid induction of inflammatory lipid mediators by the inflammasome in vivo[J]. Nature, 2012, 490(7418): 107-111. DOI: 10.1038/nature11351.
[3]	MOUCHLIS VD, DENNIS EA. Phospholipase A2 catalysis and lipid mediator lipidomics[J]. Biochim Biophys Acta Mol Cell Biol Lipids, 2019, 1864(6): 766-771. DOI: 10.1016/j.bbalip.2018.08.010.
[4]	LEUTI A, FAZIO D, FAVA M, et al. Bioactive lipids, inflammation and chronic diseases[J]. Adv Drug Deliv Rev, 2020, 159: 133-169. DOI: 10.1016/j.addr.2020.06.028.
[5]	BOSMA KJ, KAISER CE, KIMPLE ME, et al. Effects of arachidonic acid and its metabolites on functional beta-cell mass[J]. Metabolites, 2022, 12(4): 342. DOI: 10.3390/metabo12040342.
[6]	NI KD, LIU JY. The functions of cytochrome P450 ω-hydroxylases and the associated eicosanoids in inflammation-related diseases[J]. Front Pharmacol, 2021, 12: 716801. DOI: 10.3389/fphar.2021.716801.
[7]	KAUR B, SINGH P. Inflammation: Biochemistry, cellular targets, anti-inflammatory agents and challenges with special emphasis on cyclooxygenase-2[J]. Bioorg Chem, 2022, 121: 105663. DOI: 10.1016/j.bioorg.2022.105663.
[8]	AOKI T, NARUMIYA S. Prostaglandins and chronic inflammation[J]. Trends Pharmacol Sci, 2012, 33(6): 304-311. DOI: 10.1016/j.tips.2012.02.004.
[9]	CHIURCHIÙ V, LEUTI A, MACCARRONE M. Bioactive lipids and chronic inflammation: Managing the fire within[J]. Front Immunol, 2018, 9: 38. DOI: 10.3389/fimmu.2018.00038.
[10]	SERHAN CN. Pro-resolving lipid mediators are leads for resolution physiology[J]. Nature, 2014, 510(7503): 92-101. DOI: 10.1038/nature13479.
[11]	SERHAN CN, DALLI J, KARAMNOV S, et al. Macrophage proresolving mediator maresin 1 stimulates tissue regeneration and controls pain[J]. FASEB J, 2012, 26(4): 1755-1765. DOI: 10.1096/fj.11-201442.
[12]	WERZ O, GERSTMEIER J, LIBREROS S, et al. Human macrophages differentially produce specific resolvin or leukotriene signals that depend on bacterial pathogenicity[J]. Nat Commun, 2018, 9(1): 59. DOI: 10.1038/s41467-017-02538-5.
[13]	ASATRYAN A, BAZAN NG. Molecular mechanisms of signaling via the docosanoid neuroprotectin D1 for cellular homeostasis and neuroprotection[J]. J Biol Chem, 2017, 292(30): 12390-12397. DOI: 10.1074/jbc.R117.783076.
[14]	CHIURCHIÙ V, LEUTI A, DALLI J, et al. Proresolving lipid mediators resolvin D1, resolvin D2, and maresin 1 are critical in modulating T cell responses[J]. Sci Transl Med, 2016, 8(353): 353ra111. DOI: 10.1126/scitranslmed.aaf7483.
[15]	SERHAN CN, LEVY BD. Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators[J]. J Clin Invest, 2018, 128(7): 2657-2669. DOI: 10.1172/JCI97943.
[16]	PEREZ-HERNANDEZ J, CHIURCHIÙ V, PERRUCHE S, et al. Regulation of T-Cell immune responses by pro-resolving lipid mediators[J]. Front Immunol, 2021, 12: 768133. DOI: 10.3389/fimmu.2021.768133.
[17]	SUCIU M, GRUIA AT, NICA DV, et al. Acetaminophen-induced liver injury: Implications for temporal homeostasis of lipid metabolism and eicosanoid signaling pathway[J]. Chem Biol Interact, 2015, 242: 335-344. DOI: 10.1016/j.cbi.2015.10.019.
[18]	ABDEL-GABER SA, IBRAHIM MA, AMIN EF, et al. Effect of selective versus non-selective cyclooxygenase inhibitors on ischemia-reperfusion-induced hepatic injury in rats[J]. Life Sci, 2015, 134: 42-48. DOI: 10.1016/j.lfs.2015.04.025.
[19]	HAN C, LI G, LIM K, et al. Transgenic expression of cyclooxygenase-2 in hepatocytes accelerates endotoxin-induced acute liver failure[J]. J Immunol, 2008, 181(11): 8027-8035. DOI: 10.4049/jimmunol.181.11.8027.
[20]	MISAWA H, OHASHI W, TOMITA K, et al. Prostacyclin mimetics afford protection against lipopolysaccharide/d-galactosamine-induced acute liver injury in mice[J]. Toxicol Appl Pharmacol, 2017, 334: 55-65. DOI: 10.1016/j.taap.2017.09.003.
[21]	SREERAMKUMAR V, FRESNO M, CUESTA N. Prostaglandin E2 and T cells: Friends or foes?[J]. Immunol Cell Biol, 2012, 90(6): 579-586. DOI: 10.1038/icb.2011.75.
[22]	NORTH TE, BABU IR, VEDDER LM, et al. PGE2-regulated wnt signaling and N-acetylcysteine are synergistically hepatoprotective in zebrafish acetaminophen injury[J]. Proc Natl Acad Sci U S A, 2010, 107(40): 17315-17320. DOI: 10.1073/pnas.1008209107.
[23]	WANG H, ZHANG R, ZHU Y, et al. Microsomal prostaglandin E synthase 2 deficiency is resistant to acetaminophen-induced liver injury[J]. Arch Toxicol, 2019, 93(10): 2863-2878. DOI: 10.1007/s00204-019-02543-1.
[24]	NISHIZAWA N, ITO Y, ESHIMA K, et al. Inhibition of microsomal prostaglandin E synthase-1 facilitates liver repair after hepatic injury in mice[J]. J Hepatol, 2018, 69(1): 110-120. DOI: 10.1016/j.jhep.2018.02.009.
[25]	WANG J, LIU Y, DING H, et al. Mesenchymal stem cell-secreted prostaglandin E2 ameliorates acute liver failure via attenuation of cell death and regulation of macrophage polarization[J]. Stem Cell Res Ther, 2021, 12(1): 15. DOI: 10.1186/s13287-020-02070-2.
[26]	ITO S, ITO Y, KATAGIRI H, et al. Leukotriene B4/leukotriene B4 receptor pathway is involved in hepatic microcirculatory dysfunction elicited by endotoxin[J]. Shock, 2008, 30(1): 87-91. DOI: 10.1097/shk.0b013e31815d06a1.
[27]	LI L, LIU YR, GAO S, et al. Inhibition of 5-lipoxygenase pathway attenuates acute liver failure by inhibiting macrophage activation[J]. J Immunol Res, 2014, 2014: 697560. DOI: 10.1155/2014/697560.
[28]	TITOS E, CLÀRIA J, PLANAGUMÀ A, et al. Inhibition of 5-lipoxygenase-activating protein abrogates experimental liver injury: role of Kupffer cells[J]. J Leukoc Biol, 2005, 78(4): 871-878. DOI: 10.1189/jlb.1204747.
[29]	QIN XB, ZHANG RZ, WU C, et al. Immunotherapy for acute-on-chronic liver failure[J]. J Clin Hepatol, 2021, 37(11): 2696-2700. DOI: 10.3969/j.issn.1001-5256.2021.11.046. 覃小宾, 张荣臻, 吴聪, 等. 慢加急性肝衰竭的免疫治疗[J]. 临床肝胆病杂志, 2021, 37(11): 2696-2700. DOI: 10.3969/j.issn.1001-5256.2021.11.046.
[30]	LÓPEZ-VICARIO C, CHECA A, URDANGARIN A, et al. Targeted lipidomics reveals extensive changes in circulating lipid mediators in patients with acutely decompensated cirrhosis[J]. J Hepatol, 2020, 73(4): 817-828. DOI: 10.1016/j.jhep.2020.03.046.
[31]	ALCARAZ-QUILES J, CASULLERAS M, OETTL K, et al. Oxidized albumin triggers a cytokine storm in leukocytes through P38 mitogen-activated protein kinase: Role in systemic inflammation in decompensated cirrhosis[J]. Hepatology, 2018, 68(5): 1937-1952. DOI: 10.1002/hep.30135.
[32]	HUANG XP, WANG Y, CHEN L, et al. Elevated serum prostaglandin E2 predicts the risk of infection in hepatitis B virus-related acute-on-chronic liver failure patients[J]. Asian Pac J Trop Med, 2017, 10(9): 916-920. DOI: 10.1016/j.apjtm.2017.08.008.
[33]	MAINI AA, BECARES N, CHINA L, et al. Monocyte dysfunction in decompensated cirrhosis is mediated by the prostaglandin E2-EP4 pathway[J]. JHEP Rep, 2021, 3(6): 100332. DOI: 10.1016/j.jhepr.2021.100332.
[34]	WANG Y, CHEN C, QI J, et al. Altered PGE2-EP2 is associated with an excessive immune response in HBV-related acute-on-chronic liver failure[J]. J Transl Med, 2019, 17(1): 93. DOI: 10.1186/s12967-019-1844-0.
[35]	JIANG X, LI Z, JIANG S, et al. Lipoxin A4 exerts protective effects against experimental acute liver failure by inhibiting the NF-κB pathway[J]. Int J Mol Med, 2016, 37(3): 773-780. DOI: 10.3892/ijmm.2016.2483.
[36]	CHEN X, GONG X, JIANG R, et al. Resolvin D1 attenuates CCl4-induced acute liver injury involving up-regulation of HO-1 in mice[J]. Immunopharmacol Immunotoxicol, 2016, 38(2): 61-67. DOI: 10.3109/08923973.2015.1115517.
[37]	SORDI R, CHIAZZA F, COLLOTTA D, et al. Resolvin D1 attenuates the organ injury associated with experimental hemorrhagic shock[J]. Ann Surg, 2021, 273(5): 1012-1021. DOI: 10.1097/SLA.0000000000003407.
[38]	MURAKAMI T, SUZUKI K, TAMURA H, et al. Suppressive action of resolvin D1 on the production and release of septic mediators in D-galactosamine-sensitized endotoxin shock mice[J]. Exp Ther Med, 2011, 2(1): 57-61. DOI: 10.3892/etm.2010.170.
[39]	CLÀRIA J, STAUBER RE, COENRAAD MJ, et al. Systemic inflammation in decompensated cirrhosis: Characterization and role in acute-on-chronic liver failure[J]. Hepatology, 2016, 64(4): 1249-1264. DOI: 10.1002/hep.28740.
[40]	ZHANG IW, CURTO A, LÓPEZ-VICARIO C, et al. Mitochondrial dysfunction governs immunometabolism in leukocytes of patients with acute-on-chronic liver failure[J]. J Hepatol, 2022, 76(1): 93-106. DOI: 10.1016/j.jhep.2021.08.009.
[41]	CLÀRIA J, FLORES-COSTA R, DURAN-GVELL M, et al. Proresolving lipid mediators and liver disease[J]. Biochim Biophys Acta Mol Cell Biol Lipids, 2021, 1866(11): 159023. DOI: 10.1016/j.bbalip.2021.159023.
[42]	MOREAU R, CLÀRIA J, AGUILAR F, et al. Blood metabolomics uncovers inflammation-associated mitochondrial dysfunction as a potential mechanism underlying ACLF[J]. J Hepatol, 2020, 72(4): 688-701. DOI: 10.1016/j.jhep.2019.11.009.
[43]	GU J, LUO L, WANG Q, et al. Maresin 1 attenuates mitochondrial dysfunction through the ALX/cAMP/ROS pathway in the cecal ligation and puncture mouse model and sepsis patients[J]. Lab Invest, 2018, 98(6): 715-733. DOI: 10.1038/s41374-018-0031-x.
[44]	HECKER M, SOMMER N, FOCH S, et al. Resolvin E1 and its precursor 18R-HEPE restore mitochondrial function in inflammation[J]. Biochim Biophys Acta Mol Cell Biol Lipids, 2018, 1863(9): 1016-1028. DOI: 10.1016/j.bbalip.2018.06.011.
[45]	OKADA L, OLIVEIRA CP, STEFANO JT, et al. Omega-3 PUFA modulate lipogenesis, ER stress, and mitochondrial dysfunction markers in NASH - Proteomic and lipidomic insight[J]. Clin Nutr, 2018, 37(5): 1474-1484. DOI: 10.1016/j.clnu.2017.08.031.
[46]	YANG J, FERNÁNDEZ-GALILEA M, MARTÍNEZ-FERNÁNDEZ L, et al. Oxidative stress and non-alcoholic fatty liver disease: Effects of Omega-3 fatty acid supplementation[J]. Nutrients, 2019, 11(4). DOI: 10.3390/nu11040872.
[47]	KULKARNI AV, ANAND L, VYAS AK, et al. Omega-3 fatty acid lipid emulsions are safe and effective in reducing endotoxemia and sepsis in acute-on-chronic liver failure: An open-label randomized controlled trial[J]. J Gastroenterol Hepatol, 2021, 36(7): 1953-1961. DOI: 10.1111/jgh.15400.