非酒精性脂肪肝发病机制——“二次打击”学说研究进展

董姝; 刘平; 孙明瑜

非酒精性脂肪肝发病机制——“二次打击”学说研究进展

1. 上海中医药大学附属曙光医院
2. 上海中医药大学肝病研究所肝肾疾病病证教育部重点实验室
3. 上海中医药大学
4. 上海高校中医内科学E-研究院

基金项目:

上海中医药大学首届杏林学者、上海市重点科技攻关项目(No.11DZ1971702)；上海市教育委员会E-研究院建设计划项目(No.E03008)；上海高校创新团队建设项目、国家中医药管理局中医肝胆病重点学科、慢性肝病虚损重点研究室和上海市中医临床重点实验室资助；

详细信息

中图分类号: R575.5
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出版历程
- 出版日期: 2012-07-20

Role of “two-hit” in non-alcoholic fatty liver disease

Research funding:

摘要

摘要: 非酒精性脂肪肝(NAFLD)是肝脏系统中一类最为普遍的肝脏疾病。近年来,随着生活水平的提高,其发病率也逐年上升。由于NAFLD发病的隐匿性,其具体的发病机制目前仍不清楚,"二次打击"学说在其中的重要地位已得到一致认可。现就NAFLD发病机制与"二次打击"相关的细胞因子、代谢以及免疫方面等因素作一综述。
- 脂肪肝 /
- 二次打击
Abstract: The manifestation of non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to non-alcoholic steatohepatitis.The "two-hit" hypothesis of NAFLD is widely accepted as an accurate description of the underlying pathogenic mechanism.The first hit is an increased fat flux to the liver, which predisposes a patient to the second hit, in which increased mitochondrial free fatty acid oxidation promotes oxidative stress, lipoperoxidation, and increased reactive oxygen species.In this review, we discuss the roles of immune-and inflammation-related factors, such as cytokines, and metabolic factors in the "two-hit" process of NAFLD.
- fatty liver /
- two-hit

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参考文献(42)

[1]Forbes S, Taylor-Robinson SD, Patel N, et al.Increasedprevalence of non-alcoholic fatty liver disease in Europeanwomen with a history of gestational diabetes[J].Diabetolo-gia, 2011, 54 (3) :641-647.

[2]Yatsuji S, Hashimoto E, Kaneda H, et al.Diagnosing auto-immune hepatitis in nonalcoholic fatty liver disease:is the In-ternational Autoimmune Hepatitis Group scoring system use-ful?[J].J Gastroenterol, 2005, 40 (12) :1130-1138.

[3]Chen ZW, Chen LY, Dai HL, et al.Relationship between al-anine aminotransferase levels and metabolic syndrome innonalcoholic fatty liver disease[J].J Zhejiang Univ Sci B, 2008, 9 (8) :616-622.

[4]Matafome P, Nunes E, Louro T, et al.A role for atorvastatinand insulin combination in protecting from liver injury in a modelof type 2 diabetes with hyperlipidemia[J].Naunyn-Schmiede-berg’s Arch Pharmacol, 2009, 379 (3) :241-251.

[5]Alkhouri N, Tamimi TA, Yerian L, et al.The inflamed liverand atherosclerosis:a link between histologic severity ofnonalcoholic fatty liver disease and increased cardiovascularrisk[J].Dig Dis Sci, 2010, 55 (9) :2644-2650.

[6]Aygun C, Kocaman O, Sahin T, et al.Evaluation of metabol-ic syndrome frequency and carotid artery intima-mediathickness as risk factors for atherosclerosis in patients withnonalcoholic fatty liver disease[J].Dig Dis Sci, 2008, 53 (5) :1352-1357.

[7]Schnedl WJ, Wallner SJ, Piswanger C, et al.Glycated he-moglobin and liver disease in diabetes mellitus[J].WienMed Wochenschr, 2005, 155 (17-18) :411-415.

[8]Inoue H, Sameshima N, Ishida T, et al.Vulnerability of ex-perimentally induced fatty liver to heat stress in rats[J].JGastroenterol, 2006, 41 (1) :55-61.

[9]Caballería L, Auladell MA, Torán P, et al.Prevalence andfactors associated with the presence of nonalcoholic fatty liv-er disease in an apparently healthy adult population in prima-ry care units[J].BMC Gastroenterology, 2007, 5 (7) :41.

[10]Carazo A, León J, Casado J, et al.Hepatic expression of adi-ponectin receptors increases with non-alcoholic fatty liver dis-ease progression in morbid obesity in correlation with glutathi-one peroxidase 1[J].Obes Surg, 2011, 21 (4) :492-500.

[11]Sachdev MS, Riely CA, Madan AK, et al.Nonalcoholic fattyliver disease of obesity mankanwal[J].Obesity Surgery, 2006, 16 (11) :1412-1419.

[12]Ping XU, Zhang XG, Li YM, et al.Research on the protec-tion effect of pioglitazone for non-alcoholic fatty liver dis-ease (NAFLD) in rats[J].J Zhejiang Univ Science B, 2006, 7 (8) :627-633.

[13]Lewis JR, Mohanty SR.Nonalcoholic fatty liver disease:a re-view and update[J].Dig Dis Sci, 2010, 55 (3) :560-578.

[14]Schindhelm RK, Diamant M, Heine RJ, et al.Non-alcohol-ic Fatty Liver Disease and Cardiovascular Disease Risk[J].Current Diabetes Reports, 2007, 7:181-187.

[15]Buechler C, Wanninger J, Neumeier M, et al.Adiponectin, a key adipokine in obesity related liver diseases[J].World JGastroenterol, 2011, 17 (23) :2801-2811.

[16]Duvnjak M, Lerotic I, Barsic N, et al.Pathogenesis and man-agement issues for non-alcoholic fatty liver disease[J].WorldJ Gastroenterol, 2007, 13 (34) :4539-4550.

[17]Stefan N, Machicao F, Staiger H, et al.Polymorphisms inthe gene encoding adiponectin receptor 1 are associated withinsulin resistance and high liver fat[J].Diabetologia, 2005, 48 (11) :2282-2291.

[18]Ozkol M, Ersoy B, Kasirga E, et al.Metabolic predictors forearly identification of fatty liver using doppler and B-modeultrasonography in overweight and obese adolescents[J].Eur J Pediatr, 2010, 169 (11) :1345-1352.

[19]Harte AL, Silva NFD, Creely SJ, et al.Elevated endotoxinlevels in non-alcoholic fatty liver disease[J].J Inflamm, 2010, 7:15.

[20]Chen X, Zhang C, Zhao M, et al.Melatonin alleviates li-popolysaccharide-induced hepatic SREBP-1c activationand lipid accumulation in mice[J].J Pineal Res, 2011, 51 (4) :416-425.

[21]Jornayvaz FR, Birkenfeld AL, Jurczak MJ, et al.Hepatic in-sulin resistance in mice with hepatic overexpression of diacyl-glycerol acyltransferase 2[J].Proc Natl Acad Sci USA, 2011, 108 (14) :5748-5752.

[22]Yndestad A, Haukeland JW, Dahl TB, et al.Activin A innonalcoholic fatty liver disease[J].Vitam Horm, 2011, 85:323-342.

[23]Argentou M, Tiniakos DG, Karanikolas M, et al.Adipokineserum levels are related to liver histology in severely obesepatients undergoing bariatric surgery[J].Obes Surg, 2009, 19 (9) :1313-1323.

[24]Fernández-Real JM, Ortega F, Gómez-Ambrosi J, et al.Circulating osteocalcin concentrations are associated with pa-rameters of liver fat infiltration and increase in parallel to de-creased liver enzymes after weight loss[J].Osteoporos Int, 2010, 21 (12) :2101-2107.

[25]Martínez-Clemente M, Clària J, Titos E, et al.The 5-li-poxygenase/leukotriene pathway in obesity, insulin resist-ance, and fatty liver disease[J].Curr Opin Clin Nutr MetabCare, 2011, 14 (4) :347-353.

[26]Espe M, Rathore RM, Du ZY, et al.Methionine limitation resultsin increased hepatic FAS activity, higher liver 18:1 to 18:0 fattyacid ratio and hepatic TAG accumulation in Atlantic salmon, Salmosalar[J].Amino Acids, 2010, 39 (2) :449-460.

[27]Botezelli JD, Mora RF, Dalia RA, et al.Exercise counteractsfatty liver disease in rats fed on fructose-rich diet[J].Lip-ids in Health and Disease, 2010, 9:116.

[28]Du D, Shi YH, Le GW, et al.Oxidative stress induced by high-glucose diet in liver of C57BL/6J mice and its underlyingmechanism[J].Mol Biol Rep, 2010, 37 (8) :3833-3839.

[29]Duseja A.Nonalcoholic fatty liver disease in India-a lotdone, yet more required![J].Indian J Gastroenterol, 2010, 29 (6) :217-225.

[30]Ferreira-Hermosillo A, Torres-Duran PV, Juarez-OropezaMA, et al.Hepatoprotective effects of Spirulina maxima inpatients with non-alcoholic fatty liver disease:a case series[J].J Med Case Reports, 2010, 4:103.

[31]Wolf AM, Busch B, Kuhlmann HW, et al.Histological changesin the liver of morbidly obese patients:correlation with metabol-ic parameters[J].Obes Surg, 2005, 15 (2) :228-237.

[32]Cardoso AR, Costa JVC, Kowaltowski AJ, et al.Effects of ahigh fat diet on liver mitochondria:increased ATP-sensitiveK+channel activity and reactive oxygen species generation[J].J Bioenerg Biomembr, 2010, 42 (3) :245-253.

[33]Zhan YT, An W.Roles of liver innate immune cells in nonal-coholic fatty liver disease[J]World J Gastroenterol, 2010, 16 (37) :4652-4660.

[34]Sa'nchez-Lozada LG, Mu W, Roncal C, et al.Comparisonof free fructose and glucose to sucrose in the ability to causefatty liver[J].Eur J Nutr, 2010, 49 (1) :1-9.

[35]Lim JS, Mietus-Snyder M, Valente A, et al.The role offructose in the pathogenesis of NAFLD and the metabolicsyndrome[J].Nat Rev Gastroenterol Hepatol, 2010, 7 (5) :251-264.

[36]Aller R, Luis DAD, Izaola O, et al.Influence of visfatin onhistopathological changes of non-alcoholic fatty liver disease[J].Dig dis sci, 2009, 54 (8) :1772-1777.

[37]Koda M, Kawakami M, Murawaki Y, et al.The impact ofvisceral fat in nonalcoholic fatty liver disease:cross-sec-tional and longitudinal studies[J].J Gastroenterol, 2007, 42 (11) :897-903.

[38]Baranova A, Schlauch K, Elariny H, et al.Gene expressionpatterns in hepatic tissue and visceral adipose tissue of pa-tients with non-alcoholic fatty liver disease[J].Obes Surg, 2007, 17 (8) :1111-1118.

[39]Ma KL, Ruan XZ, Powis SH, et al.Inflammatory stress ex-acerbates lipid accumulation in hepatic cells and fatty livers ofapolipoprotein E knockout mice[J].Hepatology, 2008, 48 (3) :770-781.

[40]Roth CL, Elfers CT, Figlewicz DP, et al.Vitamin D deficien-cy in obese rats exacerbates NAFLD and increases hepaticresistin and toll-like receptor activation[J].Hepatology, 2012, 55 (4) :1103-1111.

[41]Botella-Carretero JI, Balsa JA, Vázquez C, et al.Retinoland alpha-tocopherol in morbid obesity and nonalcoholic fat-ty liver disease[J].Obes Surg, 2010, 20 (1) :69-76.

[42]Gentile CL, Pagliassotti MJ.The role of fatty acids in the de-velopment and progression of nonalcoholic fatty liver disease[J].J Nutr Biochem, 2008, 19 (9) :567-576.

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