PDF下载 ( 290 KB)
Research advances in the pathogenesis of alcoholic liver disease
-
摘要:
酒精性肝病（ALD）是肝功能障碍和肝相关疾病死亡的常见原因,给人类健康和社会发展带来了极大危害。氧化应激、肠道微生物改变、遗传变异、自噬抑制、microRNA等许多因素被认为参与了ALD的发生发展。现就这些因素在ALD中的作用机制作一概述,以期为治疗ALD和发现新的药物靶点提供依据。
Abstract:Alcoholic liver disease( ALD) is a common cause of liver dysfunction and death due to liver-related diseases,which brings great harm to human health and social development. Many factors are involved in the development and progression of ALD,such as oxidative stress,change in gut microbiota,genetic variation,autophagy inhibition,and microRNAs. This article summarizes the mechanism of action of these factors in ALD,in order to provide a basis for the treatment of ALD and the discovery of new drug targets.
-
[1] OMATA M,CHENG AL,KOKUDO N,et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma:A 2017 update[J]. Hepatol Int,2017,11(4):317-370. [2] YAN H,LU XL,GAO YQ,et al. Epidemiological investigation of fatty liver disease in Northwest China[J]. Chin J Hepatol,2015,23(8):622-627.(in Chinese)延华，鲁晓岚，高艳琼，等．西北地区脂肪性肝病的流行病学调查研究[J]．中华肝脏病杂志，2015,23(8):622-627. [3] 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. [4] MCCLAIN C,VATSALYA V,CAVE M. Role of zinc in the development/progression of alcoholic liver disease[J]. Curr Treat Options Gastroenterol,2017,15(2):285-295. [5] AJAKAIYE M,JACOB A,WU R,et al. Alcohol and hepatocyteKupffer cell interaction(review)[J]. Mol Med Rep,2011,4(4):597-602. [6] ZHU H,JIA Z,MISRA H,et al. Oxidative stress and redox signaling mechanisms of alcoholic liver disease:Updated experimental and clinical evidence[J]. J Dig Dis,2012,13(3):133-142. [7] CENI E,MELLO T,GALLI A. Pathogenesis of alcoholic liver disease:Role of oxidative metabolism[J]. World J Gastroenterol,2014,20(47):17756-17772. [8] TESCHKE R. Alcoholic steatohepatitis(ASH)and alcoholic hepatitis(AH):Cascade of events,clinical aspects,and pharmacotherapy options[J]. Expert Opin Pharmacother,2018,19(8):779-793. [9] KALYANARAMAN B. Teaching the basics of redox biology to medical and graduate students:Oxidants,antioxidants and disease mechanisms[J]. Redox Biol,2013,1:244-257. [10] TANG Y,LI Y,YU H,et al. Quercetin attenuates chronic ethanol hepatotoxicity:Implication of “free”iron uptake and release[J]. Food Chem Toxicol,2014,67:131-138. [11] DI LUZIO NR. A mechanism of the acute ethanol-induced fatty liver and the modification of liver injury by antioxidants[J]. Am J Pharm Sci Support Public Health,1966,15(1 Pt1):50-63. [12] GALICIA-MORENO M,GUTIRREZ-REYES G. The role of oxidative stress in the development of alcoholic liver disease[J]. Rev Gastroenterol Mex,2014,79(2):135-144. [13] PROCTOR LM. The Human Microbiome Project in 2011 and beyond[J]. Cell Host Microbe,2011,10(4):287-291. [14] YAN AW,FOUTS DE,BRANDL J,et al. Enteric dysbiosis associated with a mouse model of alcoholic liver disease[J].Hepatology,2011,53(1):96-105. [15] BJRKHAUG ST,AANES H,NEUPANE SP,et al. Characterization of gut microbiota composition and functions in patients with chronic alcohol overconsumption[J]. Gut Microbes,2019,10(6):663-675. [16] MUTLU EA,GILLEVET PM,RANGWALA H,et al. Colonic microbiome is altered in alcoholism[J]. Am J Physiol Gastrointest Liver Physiol,2012,302(9):g966-g978. [17] XIE G,ZHONG W,ZHENG X,et al. Chronic ethanol consumption alters mammalian gastrointestinal content metabolites[J]. J Proteome Res,2013,12(7):3297-3306. [18] SCHNABL B,BRENNER DA. Interactions between the intestinal microbiome and liver diseases[J]. Gastroenterology,2014,146(6):1513-1524. [19] LECLERCQ S,de SAEGER C,DELZENNE N,et al. Role of inflammatory pathways,blood mononuclear cells,and gutderived bacterial products in alcohol dependence[J]. Biol Psychiatry,2014,76(9):725-733. [20] YANG AM,INAMINE T,HOCHRATH K,et al. Intestinal fungi contribute to development of alcoholic liver disease[J]. J Clin Invest,2017,127(7):2829-2841. [21] STICKEL F,DATZ C,HAMPE J,et al. Pathophysiology and management of alcoholic liver disease:Update 2016[J]. Gut Liver,2017,11(2):173-188. [22] DODGE NC,JACOBSON JL,JACOBSON SW. Protective effects of the alcohol dehydrogenase-ADH1B*3 allele on attention and behavior problems in adolescents exposed to alcohol during pregnancy[J]. Neurotoxicol Teratol,2014,41:43-50. [23] AGRAWAL A,BIERUT LJ. Identifying genetic variation for alcohol dependence[J]. Alcohol Res,2012,34(3):274-281. [24] KOLLA BP,SCHNEEKLOTH TD,BIERNACKA J,et al. PNPLA3association with alcoholic liver disease in a cohort of heavy drinkers[J]. Alcohol Alcohol,2018,53(4):357-360. [25] ZHANG Y,GUO T,YANG F,et al. Single-nucleotide rs738409polymorphisms in the PNPLA3 gene are strongly associated with alcoholic liver disease in Han Chinese males[J]. Hepatol Int,2018,12(5):429-437. [26] FRIEDRICH K,WANNHOFF A,KATTNER S,et al. PNPLA3 in end-stage liver disease:Alcohol consumption,hepatocellular carcinoma development,and transplantation-free survival[J]. J Gastroenterol Hepatol,2014,29(7):1477-1484. [27] DING WX,LI M,CHEN X,et al. Autophagy reduces acute ethanol-induced hepatotoxicity and steatosis in mice[J].Gastroenterology,2010,139(5):1740-1752. [28] WILLIAMS JA,DING WX. A mechanistic review of mitophagy and its role in protection against alcoholic liver disease[J]. Biomolecules,2015,5(4):2619-2642. [29] DING WX. Role of autophagy in liver physiology and pathophysiology[J]. World J Biol Chem,2010,1(1):3-12. [30] LIN CW,ZHANG H,LI M,et al. Pharmacological promotion of autophagy alleviates steatosis and injury in alcoholic and non-alcoholic fatty liver conditions in mice[J]. J Hepatol,2013,58(5):993-999. [31] HARADA M. Autophagy is involved in the elimination of intracellular inclusions,Mallory-Denk bodies,in hepatocytes[J].Med Mol Morphol,2010,43(1):13-18. [32] THOMES PG,TRAMBLY CS,FOX HS,et al. Acute and chronic ethanol administration differentially modulate hepatic autophagy and transcription factor EB[J]. Alcohol Clin Exp Res,2015,39(12):2354-2363. [33] CHAO X,WANG S,ZHAO K,et al. Impaired TFEB-mediated lysosome biogenesis and autophagy promote chronic ethanol-induced liver injury and steatosis in mice[J]. Gastroenterology,2018,155(3):865-879. [34] SCHULZE RJ,RASINENI K,WELLER SG,et al. Ethanol exposure inhibits hepatocyte lipophagy by inactivating the small guanosine triphosphatase Rab7[J]. Hepatol Commun,2017,1(2):140-152. [35] RASINENI K,DONOHUE TM Jr,THOMES PG,et al. Ethanol-induced steatosis involves impairment of lipophagy,associated with reduced Dynamin2 activity[J]. Hepatol Commun,2017,1(6):501-512. [36] BLAYA D,COLL M,RODRIGO-TORRES D,et al. Integrative microRNA profiling in alcoholic hepatitis reveals a role for microRNA-182 in liver injury and inflammation[J]. Gut,2016,65(9):1535-1545. [37] BALA S,CSAK T,SAHA B,et al. The pro-inflammatory effects of miR-155 promote liver fibrosis and alcohol-induced steatohepatitis[J]. J Hepatol,2016,64(6):1378-1387. [38] SATISHCHANDRAN A,AMBADE A,RAO S,et al. MicroRNA122,regulated by GRLH2,protects livers of mice and patients from ethanol-induced liver disease[J]. Gastroenterology,2018,154(1):238-252. [39] LI M,HE Y,ZHOU Z,et al. MicroRNA-223 ameliorates alcoholic liver injury by inhibiting the IL-6-p47phox-oxidative stress pathway in neutrophils[J]. Gut,2017,66(4):705-715. [40] WANG S,DING WX. A small RNA in neutrophils protects against acute-on-chronic alcoholic liver injury[J]. Gut,2017,66(4):565-566. [41] ZHAO YX,SUN YY,HUANG AL,et al. MicroRNA-200a induces apoptosis by targeting ZEB2 in alcoholic liver disease[J]. Cell Cycle,2018,17(2):250-262. [42] LI HH,TYBURSKI JB,WANG YW,et al. Modulation of fatty acid and bile acid metabolism by peroxisome proliferator-activated receptorαprotects against alcoholic liver disease[J].Alcohol Clin Exp Res,2014,38(6):1520-1531. [43] HUANG CK,YU T,de la MONTE SM,et al. Restoration of Wnt/β-catenin signaling attenuates alcoholic liver disease progression in a rat model[J]. J Hepatol,2015,63(1):191-198. [44] SEITZ HK,BATALLER R,CORTEZ-PINTO H,et al. Alcoholic liver disease[J]. Nat Rev Dis Primers,2018,4(1):16. [45] OSNA NA,DONOHUE TM Jr,KHARBANDA KK. Alcoholic liver disease:Pathogenesis and current management[J]. Alcohol Res,2017,38(2):147-161. -
本文二维码
计量
- 文章访问数: 859
- HTML全文浏览量: 83
- PDF下载量: 127
- 被引次数: 0
下载:
