Mouse model of chronic and binge ethanol feeding (the NIAAA model)

被引:938
作者
Bertola, Adeline [1 ]
Mathews, Stephanie [1 ]
Ki, Sung Hwan [1 ]
Wang, Hua [1 ]
Gao, Bin [1 ]
机构
[1] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA
关键词
ALCOHOLIC LIVER-DISEASE; OXIDATIVE STRESS; INTRAGASTRIC INFUSION; HEPATIC STEATOSIS; FATTY LIVER; TNF-ALPHA; FED MICE; INJURY; PATHOGENESIS; STEATOHEPATITIS;
D O I
10.1038/nprot.2013.032
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Chronic alcohol consumption is a leading cause of chronic liver disease worldwide, leading to cirrhosis and hepatocellular carcinoma. Currently, the most widely used model for alcoholic liver injury is ad libitum feeding with the Lieber-DeCarli liquid diet containing ethanol for 4-6 weeks; however, this model, without the addition of a secondary insult, only induces mild steatosis, slight elevation of serum alanine transaminase (ALT) and little or no inflammation. Here we describe a simple mouse model of alcoholic liver injury by chronic ethanol feeding (10-d ad libitum oral feeding with the Lieber-DeCarli ethanol liquid diet) plus a single binge ethanol feeding. This protocol for chronic-plus-single-binge ethanol feeding synergistically induces liver injury, inflammation and fatty liver, which mimics acute-on-chronic alcoholic liver injury in patients. This feeding protocol can also be extended to chronic feeding for longer periods of time up to 8 weeks plus single or multiple binges. Chronic-binge ethanol feeding leads to high blood alcohol levels; thus, this simple model will be very useful for the study of alcoholic liver disease (ALD) and of other organs damaged by alcohol consumption.
引用
收藏
页码:627 / 637
页数:11
相关论文
共 44 条
[1]   Alcoholic liver disease: pathogenesis and new targets for therapy [J].
Altamirano, Jose ;
Bataller, Ramon .
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2011, 8 (09) :491-501
[2]   Elevated Activation of ERK1 and ERK2 Accompany Enhanced Liver Injury Following Alcohol Binge in Chronically Ethanol-Fed Rats [J].
Aroor, Annayya R. ;
Jackson, Daniel E. ;
Shukla, Shivendra D. .
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 2011, 35 (12) :2128-2138
[3]   Plasminogen activator inhibitor-1 deficient mice are protected from angiotensin II-induced fibrosis [J].
Beier, Juliane I. ;
Kaiser, J. Phillip ;
Guo, Luping ;
Martinez-Maldonado, Manuel ;
Arteel, Gavin E. .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2011, 510 (01) :19-26
[4]   Advances in alcoholic liver disease [J].
Beier J.I. ;
Arteel G.E. ;
McClain C.J. .
Current Gastroenterology Reports, 2011, 13 (1) :56-64
[5]   Drinking habits as cofactors of risk for alcohol induced liver damage [J].
Bellentani, S ;
Saccoccio, G ;
Costa, G ;
Tiribelli, C ;
Manenti, F ;
Sodde, M ;
Croce, LS ;
Sasso, F ;
Pozzato, G ;
Cristianini, G ;
Brandi, G ;
Armocida, C ;
De Martin, C ;
Ferretti, I ;
Figlioli, GF ;
Fratti, N ;
Manenti, AL ;
Marchegiano, P ;
Messori, B ;
Passamonti, S ;
Poppi, C ;
Sassatelli, R .
GUT, 1997, 41 (06) :845-850
[6]   Rodent models of alcoholic liver disease: Of mice and men [J].
Brandon-Warner, Elizabeth ;
Schrum, Laura W. ;
Schmidt, C. Max ;
McKillop, Iain H. .
ALCOHOL, 2012, 46 (08) :715-725
[7]   Chronic Ethanol Feeding Accelerates Hepatocellular Carcinoma Progression in a Sex-Dependent Manner in a Mouse Model of Hepatocarcinogenesis [J].
Brandon-Warner, Elizabeth ;
Walling, Tracy L. ;
Schrum, Laura W. ;
McKillop, Iain H. .
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 2012, 36 (04) :641-653
[8]   The impact of CYP2E1 on the development of alcoholic liver disease as studied in a transgenic mouse model [J].
Butura, Angelica ;
Nilsson, Kerstin ;
Morgan, Kengathevy ;
Morgan, Timothy R. ;
French, Samuel W. ;
Johansson, Inger ;
Schuppe-Koistinen, Ina ;
Ingelman-Sundberg, Magnus .
JOURNAL OF HEPATOLOGY, 2009, 50 (03) :572-583
[9]   Alcoholic Hepatitis: A Clinician's Guide [J].
Choi, Gina ;
Runyon, Bruce Allen .
CLINICS IN LIVER DISEASE, 2012, 16 (02) :371-+
[10]   Complement and Alcoholic Liver Disease: Role of C1q in the Pathogenesis of Ethanol-Induced Liver Injury in Mice [J].
Cohen, Jessica I. ;
Roychowdhury, Sanjoy ;
Mcmullen, Megan R. ;
Stavitsky, Abram B. ;
Nagy, Laura E. .
GASTROENTEROLOGY, 2010, 139 (02) :664-674