自噬与氧化应激在非酒精性脂肪性肝病发病机制中的关系

周帆; 彭君伟; 范伏岗; 蒋元烨; 曹勤

doi:10.3969/j.issn.1001-5256.2018.08.048

自噬与氧化应激在非酒精性脂肪性肝病发病机制中的关系

DOI: 10.3969/j.issn.1001-5256.2018.08.048

1. 上海中医药大学附属普陀医院
2. 上海中医药大学研究生院

基金项目:

国家自然科学基金(青年)项目(81703879)；上海中医药大学预算内项目(2016YSN60)；上海市普陀区中心医院专科规培院级课题(PTZP201605A)；上海中医药大学附属普陀医院人才培养项目(2016212B)；

详细信息

中图分类号: R575.5
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- 被引次数: 25
出版历程
- 收稿日期: 2018-03-23
- 出版日期: 2018-08-20

Interrelation between autophagy and oxidative stress in pathogenesis of nonalcoholic fatty liver

Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

Research funding:

摘要

摘要: 非酒精性脂肪性肝病(NAFLD)是多种因素共同作用的结果,而以氧化应激为中心的"第二次打击"是NAFLD进展的关键因素。自噬作为近年来的研究热点,越来越多的证据显示自噬在肝细胞脂质代谢、炎症反应与肝纤维化中发挥重要作用,且与氧化应激有着密切关系。结合当前国内外最新研究成果分别从自噬与NAFLD的关系、氧化应激与NAFLD的关系分析自噬与氧化应激在NAFLD发病机制中的相互关系,指出自噬在NAFLD发病进程中调控氧化应激的分子机制可能成为今后的研究热点,若能够阻断或者激活自噬调控氧化应激的某个关键通路,或可为干预NAFLD提供新的手段。
- 非酒精性脂肪性肝病 /
- 自噬 /
- 氧化应激 /
- 综述
Abstract: Nonalcoholic fatty liver disease ( NAFLD) is the result of the interaction between many factors, and“second hit”focusing on oxidative stress is a key factor for the progression of NAFLD. Autophagy has been a research hotspot in recent years, and more and more studies have shown that autophagy plays an important role in lipid metabolism in hepatocytes, inflammatory response, and liver fibrosis and is closely associated with oxidative stress. With reference to the latest research findings in China and foreign countries, this article analyzes the interrelation between autophagy and oxidative stress in the pathogenesis of NAFLD from the aspects of the association between autophagy and NAFLD and the association between oxidative stress and NAFLD. It is pointed out that the molecular mechanism of the regulation of oxidative stress by autophagy in the pathogenesis of NAFLD may be a research hotspot in future, and blockade or activation of a key pathway involved in the regulation of oxidative stress by autophagy may provide a new method for the treatment of NAFLD.
- non-alcoholic fatty liver /
- autophagy /
- oxidative stress /
- review

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参考文献(37)

[1]HYEJIN Y, BONG SC.Non-alcoholic fatty liver disease pathogenesis and therapeutic approaches for non-alcoholic fatty liver disease[J].World J Hepatol, 2014, 6 (11) :800-811.

[2]XIN SL, XU KS.A new understanding of the pathogenesis of nonalcoholic fatty liver disease[J].J Clin Hepatol, 2017, 33 (8) :1581-1583. (in Chinese) 辛晟梁, 徐可树.非酒精性脂肪性肝病发病机制新认识[J].临床肝胆病杂志, 2017, 33 (8) :1581-1583.

[3]CZAJA MJ.Functions of autophagy in hepatic and pancreatic physiology and disease[J].Gastroenterology, 2011, 140 (7) :1895-1908.

[4]DAY CP.Non-alcoholic fatty liver disease:A massive problem[J].Clin Med, 2011, 11 (2) :176-178.

[5]LAVALLARD VJ, GUAL P.Autophagy and non-alcoholic fatty liver disease[J].Biomed Res Int, 2014, 2014 (4) :120179.

[6]PAN CY.Role of autophagy in liver regeneration in rats[D].Xinxiang:Henan Normal University, 2015. (in Chinese) 潘翠云.自噬在大鼠肝脏再生中的作用研究[D].新乡:河南师范大学, 2015.

[7]LICIA P, MARIA DB, FRANCESCO B, et al.Oxidative stress:New insights on the association of non-alcoholic fatty liver disease and atherosclerosis[J].World J Hepatol, 2015, 7 (10) :1325-1336.

[8]LADE A, NOON LA, FRIEDMAN SL.Contributions of metabolic dysregulation and inflammation to nonalcoholic steatohepatitis, hepatic fibrosis, and cancer[J].Curr Opin Oncol, 2014, 26 (1) :100-107.

[9]LIN QX, ZHOU DS, LIANG ZQ.Advances in research of nonalcoholic fatty liver disease and oxidative stress[J].J Trop Med, 2013, 13 (5) :657-660. (in Chinese) 林秋香, 周冬生, 梁志清.氧化应激与非酒精性脂肪肝病的研究进展[J].热带医学杂志, 2013, 13 (5) :657-660.

[10]WANG SQ, HUANG Y.Advances in research of nonalcoholic fatty liver disease[J].World Chin J Dig, 2014, 22 (23) :3410-3415. (in Chinese) 王素琴, 黄缘.非酒精性脂肪肝病的研究进展[J].世界华人消化杂志, 2014, 22 (23) :3410-3415.

[11]MARTINEZ-LOPEZ N, SINGH R.Autophagy and lipid droplets in the liver[J].Annu Rev Nutr, 2015, 35 (35) :215-237.

[12]CZAJA MJ.Function of autophagy in nonalcoholic fatty liver disease[J].Dig Dis Sci, 2016, 61 (5) :1304-1313.

[13]SETTEMBRE C, DE CR, MANSUETO G, et al.TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop[J].Nat Cell Biol, 2013, 15 (6) :647-658.

[14]LI RL, GUO ES, YANG JK, et al.1, 25 (OH) 2D3attenuates hepatic steatosis by inducing autophagy in mice[J].Obesity, 2017, 25 (3) :561-571.

[15]SAITOH T, FUJITA N, JANG MH, et al.Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1βproduction[J].Nature, 2008, 456 (7219) :264-268.

[16]MULLER TD, LEE SJ, JASTROCH M, et al.p62 linksβ-adrenergic input to mitochondrial function and thermosgenesi[J].J Clin Invest, 2013, 123 (1) :469-478.

[17]ZHANG W, JIA JD.Pathogenesis and new therapeutic targets of liver fibrosis[J].J Clin Hepatol, 2017, 33 (3) :409-412. (in Chinese) 张伟, 贾继东.肝纤维化的发病机制及治疗新靶点[J].临床肝胆病杂志, 2017, 33 (3) :409-412.

[18]HERNANDEZ-GEA V, GHIASSI-NEJAD Z, ROZENFELD R, et al.Autophagy releases lipid that promotes fibrogenesis by activated hepatic stellate cells in mice and in human tissues[J].Gastroenterology, 2012, 142 (4) :938-946.

[19]FINOMENI G, DE Z, CECCONI F.Oxidative stress and autophagy:The clash between damage and metabolic needs[J].Cell Death Differ, 2015, 22 (3) :377-388.

[20]MI Y, XIAO CX, DU QW, et al.Momordin lc couples apoptosis with autophagy in human hepatoblastoma cancer cells by reactive oxygen species (ROS) -mediated PI3K/Akt and MAPK signaling pathways[J].Free Radic Biol Med, 2016, 90:230-242.

[21]SCHERZ-SHOUVAL R, ELAZAR Z.Regulation of autophagy by ROS:Physiology and pathology[J].Trends Biochem Sci, 2011, 36 (1) :30-38.

[22]YIN XM, DING WX, GAO W.Autophagy in the liver[J].Hepatology, 2008, 47:1773-1785.

[23]WANG T, WANG QW, SONG RL, et al.Autophagy plays a cytoprotective role during cadmium-induced oxidative damage in primary neuronal cultures[J].Biol Trace Elem Res, 2015, 168 (2) :481-489.

[24]STANKOV MV, PANAYOTOVA-DIMITROVA D, LEVERKUS M, et al.Autophagy inhibition due to thymidine analogues as novel mechanism leading to hepatocyte dysfunction and lipid accumulation[J].AIDS, 2012, 26 (16) :1995-2006.

[25]PARK EJ, LEE AY, PARK S, et al.Multiple pathways are involved inpalmitic acid-induced toxicity[J].Food Chem Toxicol, 2014, 67:26-34.

[26]LI H, ZHOU B, XU L, et al.The reciprocal interaction between autophagic dysfunction and ER stress in adipose insulin resistance[J].Cell Cycle, 2014, 13 (4) :565-579.

[27]ZHAO J, SHI CZ, XU XY, et al.Effect of aerobic exercise on NASH in rats based on SIRT1 axis mitochondrial proliferation and autophagy pathway[J].J Beijing Sport Univ, 2016, 39 (1) :68-75. (in Chinese) 赵军, 史长征, 徐晓阳, 等.基于SIRT1轴的线粒体增殖和自噬通路探讨有氧运动对NASH大鼠脂肪性肝炎的影响[J].北京体育大学学报, 2016, 39 (1) :68-75.

[28]ZHOU R, YAZDI AS, MENU P, et al.A role for mitochondria in NLRP3 inflammasome activation[J].Nature, 2011, 469 (7329) :221-225.

[29] NAKAHIRA K, HASPEL JA, RATHINAM VA, et al.Autophagy proteins regulate innate immune responses by inhibiting the release of mito-chondrial DNA mediated by the NALP3 inflammasome[J].Nat Immunol, 2011, 12 (3) :222-230.

[30]TONG WX, JU LP, QIU MY, et al.Liraglutide ameliorates nonalcoholic fatty liver disease by enhancing mitochondrial architecture and promoting autophagy through the SIRT1/SIRT3-FOXO3a pathway[J].Hepatol Res, 2016, 46 (9) :933-943.

[31]ZHENG XC.Preliminary study on the protective effect and regulation mechanism of caffeine on hepatic steatosis in Zebrafish larvae[D].Guangzhou:Southern Medical University, 2015. (in Chinese) 郑新春.咖啡因对斑马鱼脂肪肝的保护作用及其机制的初步研究[D].广州:南方医科大学, 2015.

[32]DAS S, SETH RK, KUMAR A, et al.Purinergic receptor X7 is a key modulator of metabolic oxidative stress-mediated autophagy and inflammation in experimental nonalcoholic steatohepatitis[J].Am J Physiol Gastrointest Liver Physiol, 2013, 305 (12) :950-963.

[33]BRUNATI AM, PAGANO MA, BINDOLI A, et al.Thiolredox systems and protein kinases in hepatic stellate cell regulatory processes[J].Free Radic Res, 2010, 44 (4) :363-378.

[34]ZHANG J, PING J, XU LM.Resveratrol inhibits the activation of hepatic stellate cells by inducing autophagy:An analysis of mechanism[C].Guiyang:Collected Papers from the 23rd National Academic Conference on Integrated Traditional Chinese and Western Medicine Therapy for Liver Diseases, 2014:205-206. (in Chinese) 张晶, 平键, 徐列明.白藜芦醇通过诱导自噬抑制HSC活化的机制研究[C].贵阳:第二十三次全国中西医结合肝病学术会议论文汇编, 2014:205-206.

[35]ZHANG XW, MI S, LI Z, et al.Antagonism of interleukin-17A ameliorates experimental hepatic fibrosis by restoring the IL-10/STAT3-suppressed autophagy in epatocytes[J].Oncotarget, 2017, 8 (6) :9922-9934.

[36]YUAN RS, LI H, SUN JH, et al.Lipid-lowering effect and antioxidant activity of polysaccharide from Schisandra Chinensis in rats with non-alcoholic fatty liver disease induced by high-fat diet[J].J Jilin Univ:Med Edit, 2017, 43 (6) :1103-1108. (in Chinese) 苑荣爽, 李贺, 孙靖辉, 等.北五味子多糖对高脂诱导非酒精性脂肪性肝病大鼠的降血脂作用及其抗氧化活性[J].吉林大学学报:医学版, 2017, 43 (6) :1103-1108.

[37]WANG KY, LI XL, CAI YQ.Research progress of the regula tion function of autophagy in drug-induced hepatotoxicity[J].Chin J Clin Pharmacol Ther, 2017, 22 (1) :100-103. (in Chinese) 王楷杨, 李小丽, 蔡永青.自噬对药物肝毒性调控作用的研究进展[J].中国临床药理学与治疗学, 2017, 22 (1) :100-103.

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