氧化应激在肝纤维化发生发展中的作用

赵杰; 齐永芬; 鱼艳荣

doi:10.3969/j.issn.1001-5256.2019.09.040

氧化应激在肝纤维化发生发展中的作用

DOI: 10.3969/j.issn.1001-5256.2019.09.040

北京大学医学部基础医学院病原生物学系

基金项目:

国家自然科学基金(30901247)；

详细信息

中图分类号: R575.2
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出版历程
- 收稿日期: 2019-04-03
- 出版日期: 2019-09-20

Research advances in the role of oxidative stress in the development and progression of liver fibrosis

Department of Pathogen Biology, School of Basic Medical Sciences, Peking University Health Science Center

Research funding:

摘要

摘要: 肝纤维化是一种创伤愈合反应,它是由各种致病因素所致的慢性肝损伤后的纤维结缔组织沉积,若不及时治疗,会进展为肝硬化甚至肝癌,危害生命。肝星状细胞激活后转化为肌成纤维细胞进而分泌大量的细胞外基质是肝纤维化最重要的病理特征。越来越多的证据表明,氧化应激在肝纤维化的发生发展过程中发挥着重要作用,在各种疾病所致的肝纤维化过程中均有不同程度的氧化应激参与。多数情况下,氧化应激是与其他因素相互影响共同参与肝纤维化这一病理生理过程。因此,就氧化应激对肝纤维化的影响及其与其他因素如炎症、凋亡、自噬等相互作用共同影响肝纤维化的最新进展进行阐述。
- 肝硬化 /
- 氧化性应激 /
- 炎症 /
- 细胞凋亡 /
- 自噬
Abstract: Liver fibrosis is a wound-healing response and is fibrous connective tissue deposition due to chronic liver injury caused by various pathogenic factors, and without timely treatment, it may progress to life-threatening diseases such as liver cirrhosis and even liver cancer. Hepatic stellate cells are transformed into myofibroblasts after activation and then secret a large amount of extracellular matrix, which is the most important pathological feature of liver fibrosis. More and more evidence has shown that oxidative stress plays an important role in the development and progression of liver fibrosis, and oxidative stress is involved in liver fibrosis caused by various diseases. In most cases, oxidative stress interacts with other factors to promote the pathophysiological process of liver fibrosis. Therefore, this article reviews the research advances in the influence of oxidative stress on liver fibrosis and its interaction with other factors such as inflammation, apoptosis, and autophagy.
- liver cirrhosis /
- oxidative stress /
- inflammation /
- apoptosis /
- autophagy

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参考文献(57)

[1] ZUO L, ZHOU T, PANNELL BK, et al. Biological and physiological role of reactive oxygen species-the good, the bad and the ugly[J]. Acta Physiol (Oxf) , 2015, 214 (3) :329-348.

[2] LI S, TAN HY, WANG N, et al. The role of oxidative stress and antioxidants in liver diseases[J]. Int J Mol Sci, 2015, 16 (11) :26087-26124.

[3] LI S, HONG M, TAN HY, et al. Insights into the role and interdependence of oxidative stress and inflammation in liver diseases[J]. Oxid Med Cell Longev, 2016, 2016:4234061.

[4] LUANGMONKONG T. Targeting oxidative stress for the treatment of liver fibrosis[J]. Rev Physiol Biochem Pharmacol, 2018, 175:71-102.

[5] SINGAL AK, JAMPANA SC, WEINMAN SA, et al. Antioxidants as therapeutic agents for liver disease[J]. Liver Int, 2011, 31 (10) :1432-1448.

[6] URTASUN R, ROSA CDL, NIETO N, et al. Oxidative and nitrosative stress and fibrogenic response[J]. Clin Liver Dis, 2008, 12 (4) :769-790.

[7] LIN W, TSAI WL, SHAO RX, et al. Hepatitis C virus regulates transforming growth factor beta1 production through the generation of reactive oxygen species in a nuclear factor kappaBdependent manner[J]. Gastroenterology, 2010, 138 (7) :2509-2518.

[8] SHA J, ZHANG H, ZHAO Y, et al. Dexmedetomidine attenuates lipopolysaccharide-induced liver oxidative stress and cell apoptosis in rats by increasing GSK-3beta/MKP-1/Nrf2pathway activity via the alpha2 adrenergic receptor[J]. Toxicol Appl Pharmacol, 2018, 364:144-152.

[9] FARR SA, RIPLEY JL, SULTANA R, et al. Antisense oligonucleotide against GSK-3beta in brain of SAMP8 mice improves learning and memory and decreases oxidative stress:Involvement of transcription factor Nrf2 and implications for Alzheimer disease[J]. Free Radic Biol Med, 2014, 67:387-395.

[10] BATALLER R, BRENNER DA. Liver fibrosis[J]. J Clin Invest, 2005, 115 (2) :209-218.

[11] PAROLA M, PINZANI M. Liver fibrosis:Pathophysiology, pathogenetic targets and clinical issues[J]. Mol Aspects Med, 2019, 65:37-55.

[12] SUN M, KISSELEVA T. Reversibility of liver fibrosis[J]. Clin Res Hepatol Gastroenterol, 2015, 39 (Suppl 1) :s60-s63.

[13] AYDIN MM, AKCALI KC. Liver fibrosis[J]. Turk J Gastroenterol, 2018, 29 (1) :14-21.

[14] ZHANG CY, YUAN WG, HE P, et al. Liver fibrosis and hepatic stellate cells:Etiology, pathological hallmarks and therapeutic targets[J]. World J Gastroenterol, 2016, 22 (48) :10512-10522.

[15] KURDI A, HASSAN K, VENKATARAMAN B, et al. Nootkatone confers hepatoprotective and anti-fibrotic actions in a murine model of liver fibrosis by suppressing oxidative stress, inflammation, and apoptosis[J]. J Biochem Mol Toxicol, 2018, 32 (7) :e22017.

[16] ATALLAH MAA, ELAIDY SM, TAWFIK MK, et al. Assessment of the possible roles of SB-269970 versus ketanserin on carbon tetrachloride-induced liver fibrosis in rats:Oxidative stress/TGF-beta1-induced HSCs activation pathway[J].Pharmacol Rep, 2018, 70 (3) :509-518.

[17] WANG X. Gliptins suppress inflammatory macrophage activation to mitigate inflammation, fibrosis, oxidative stress, and vascular dysfunction in models of nonalcoholic steatohepatitis and liver fibrosis[J]. Antioxid Redox Signal, 2018, 28 (2) :87-109.

[18] ALTENHOFER S, RADERMACHER KA, KLEIKERS PW, et al.Evolution of NADPH oxidase inhibitors:Selectivity and mechanisms for target engagement[J]. Antioxid Redox Signal, 2015, 23 (5) :406-427.

[19] MORTEZAEE K. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and liver fibrosis:A review[J].Cell Biochem Funct, 2018, 36 (6) :292-302.

[20] HUANG J. Adoptive transfer of heme oxygenase-1 (HO-1) -modified macrophages rescues the nuclear factor erythroid 2-related factor (Nrf2) antiinflammatory phenotype in liver ischemia/reperfusion injury[J]. Mol Med, 2014, 20:448-455.

[21] JIANG JX. Reduced nicotinamide adenine dinucleotide phosphate oxidase 2 plays a key role in stellate cell activation and liver fibrogenesis in vivo[J]. Gastroenterology, 2010, 139 (4) :1375-1384.

[22] DIXON LJ, BARNES M, TANG H, et al. Kupffer cells in the liver[J]. Compr Physiol, 2013, 3 (2) :785-797.

[23] JIANG JX. Liver fibrosis and hepatocyte apoptosis are attenuated by GKT137831, a novel NOX4/NOX1 inhibitor in vivo[J]. Free Radic Biol Med, 2012, 53 (2) :289-296.

[24] SANCHO P. NADPH oxidase NOX4 mediates stellate cell activation and hepatocyte cell death during liver fibrosis development[J]. PLo S One, 2012, 7 (9) :e45285.

[25] BISWAS SK. Does the Interdependence between oxidative stress and inflammation explain the antioxidant paradox?[J]. Oxid Med Cell Longev, 2016, 2016:5698931.

[26] AMBADE A, MANDREKAR P. Oxidative stress and inflammation:Essential partners in alcoholic liver disease[J]. Int J Hepatol, 2012, 2012:853175.

[27] SNCHEZ-VALLE V, CHVEZ-TAPIA NC, MNDEZ-SNCHEZ N, et al. Role of oxidative stress and molecular changes in liver fibrosis:A review[J]. Curr Med Chem, 2012, 19:4850-4860.

[28] SUN J. Anthocyanins isolated from blueberry ameliorates CCl4induced liver fibrosis by modulation of oxidative stress, inflammation and stellate cell activation in mice[J]. Food Chem Toxicol, 2018, 120:491-499.

[29] SANCHETI S, SEO SY. Ameliorative effects of 7-methylcoumarin and 7-methoxycoumarin against CCl4-induced hepatotoxicity in rats[J]. Drug Chem Toxicol, 2013, 36 (1) :42-47.

[30] LI J. Reactive oxygen species released from hypoxic hepatocytes regulates MMP-2 expression in hepatic stellate cells[J]. Int J Mol Sci, 2011, 12 (4) :2434-2447.

[31] MENG N, XIA M, LU YQ, et al. Activation of NLRP3 inflammasomes in mouse hepatic stellate cells during Schistosoma J.infection[J]. Oncotarget, 2016, 7 (26) :39316-39331.

[32] SCHWABE RF, LUEDDE T. Apoptosis and necroptosis in the liver:A matter of life and death[J]. Nat Rev Gastroenterol Hepatol, 2018, 15 (12) :738-752.

[33] DA SILVA BDO, RAMOS LF, MORAES KCM. Molecular interplays in hepatic stellate cells:Apoptosis, senescence, and phenotype reversion as cellular connections that modulate liver fibrosis[J]. Cell Biol Int, 2017, 41 (9) :946-959.

[34] WANG K. Autophagy and apoptosis in liver injury[J]. Cell Cycle, 2015, 14 (11) :1631-1642.

[35] WANG K. Molecular mechanisms of hepatic apoptosis[J].Cell Death Dis, 2014, 5:e996.

[36] KONDO Y, ISHIGAMI A. Involvement of senescence marker protein-30 in glucose metabolism disorder and non-alcoholic fatty liver disease[J]. Geriatr Gerontol Int, 2016, 16 (Suppl1) :4-16.

[37] HU SJ, JIANG SS, ZHANG J, et al. Effects of apoptosis on liver aging[J]. World J Clin Cases, 2019, 7 (6) :691-704.

[38] MEYER JN, LEUTHNER TC, LUZ AL. Mitochondrial fusion, fission, and mitochondrial toxicity[J]. Toxicology, 2017, 391:42-53.

[39] MATSUMOTO N, EZAKI J, KOMATSU M, et al. Comprehensive proteomics analysis of autophagy-deficient mouse liver[J]. Biochem Biophys Res Commun, 2008, 368 (3) :643-649.

[40] STANKOV, MV. Autophagy inhibition due to thymidine analogues as novel mechanism leading to hepatocyte dysfunction and lipid accumulation[J]. AIDS, 2012, 26 (16) :1995-2006.

[41] LEVONEN AL, HILL BG, KANSANEN E, et al. Redox regulation of antioxidants, autophagy, and the response to stress:Implications for electrophile therapeutics[J]. Free Radic Biol Med, 2014, 71:196-207.

[42] FILOMENI G, de ZIO D, CECCONI F, et al. Oxidative stress and autophagy:The clash between damage and metabolic needs[J]. Cell Death Differ, 2015, 22 (3) :377-388.

[43] RUART M. Impaired endothelial autophagy promotes liver fibrosis by aggravating the oxidative stress response during acute liver injury[J]. J Hepatol, 2019, 70 (3) :458-469.

[44] SHIN SM, YANG JH, KI SH. Role of the Nrf2-ARE pathway in liver diseases[J]. Oxid Med Cell Longev, 2013, 2013:763257.

[45] JADEJA RN, UPADHYAY KK, DEVKAR RV. Naturally occurring Nrf2 activators:Potential in treatment of liver injury[J].Oxid Med Cell Longev, 2016, 2016:3453926.

[46] YANG JH. Bamboo stems (phyllostachys nigra variety henosis) containing polyphenol mixtures activate Nrf2 and attenuate phenylhydrazine-induced oxidative stress and liver injury[J]. Nutrients, 2019, 11 (1) :e114.

[47] GU L. Ellagic acid protects lipopolysaccharide/D-galactosamine-induced acute hepatic injury in mice[J]. Int Immunopharmacol, 2014, 22 (2) :341-345.

[48] NI HM. Nrf2 promotes the development of fibrosis and tumorigenesis in mice with defective hepatic autophagy[J]. J Hepatol, 2014, 61 (3) :617-625.

[49] CANNITO S, NOVO E, PAROLA M. Therapeutic pro-fibrogenic signaling pathways in fibroblasts[J]. Adv Drug Deliv Rev, 2017, 121:57-84.

[50] LI S, HONG M, TAN HY, et al. Insights into the role and interdependence of oxidative stressand inflammation in liver diseases[J]. Oxid Med Cell Longev, 2016, 2016:4234061.

[51] YANG JH, KIM SC, KIM KM, et al. Isorhamnetin attenuates liver fibrosis by inhibiting TGF-β/Smad signaling and relieving oxidative stress[J]. Eur J Pharmacol, 2016, 783:92-102.

[52] AFRIN R, ARUMUGAM, RAHMAN A, et al. Curcumin ameliorates liver damage and progression of NASH in NASH-HCC mouse model possibly by modulating HMGB1-NF-κB translocation[J]. Int Immunopharmacol, 2017, 44:174-182.

[53] MITCHELL S, VARGAS J, HOFFMANN A. Signaling via the NFkappaB system[J]. Wiley Interdiscip Rev Syst Biol Med, 2016, 8 (3) :227-241.

[54] BUBICI C, PAPA S, PHAM CG, et al. The NF-kappaB-mediated control of ROS and JNK signaling[J]. Histol Histopathol, 2006, 21 (1) :69-80.

[55] HUSAIN H, LATIEF U, AHMAD R. Pomegranate action in curbing the incidence of liver injury triggered by Diethylnitrosamine by declining oxidative stress via Nrf2 and NFkappaB regulation[J]. Sci Rep, 2018, 8 (1) :8606.

[56] SHI H, SHI A, DONG L, et al. Chlorogenic acid protects against liver fibrosis in vivo and in vitro through inhibition of oxidative stress[J]. Clin Nutr, 2016, 35 (6) :1366-1373.

[57] TAO GZ, LEHWALD N, JANG KY, et al. Wnt/β-catenin signaling protects mouse liver against oxidative stress-induced apoptosis through the inhibition of forkhead transcription factor FoxO3[J]. J Biol Chem, 2013, 288 (24) :17214-17224.

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