Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism NIAAA, National Institutes of Health NIH, Bethesda, Maryland, USA.
Nat Protoc. 2013 Mar;8(3):627-37. doi: 10.1038/nprot.2013.032. Epub 2013 Feb 28.
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.
慢性酒精摄入是全球范围内导致慢性肝病的主要原因，可导致肝硬化和肝细胞癌。目前，最广泛使用的酒精性肝损伤模型是自由喂养含有乙醇的 Lieber-DeCarli 液体饮食 4-6 周；然而，这种模型没有添加二次损伤，仅诱导轻度脂肪变性、血清丙氨酸转氨酶 (ALT) 轻度升高，或几乎没有炎症。在这里，我们描述了一种通过慢性乙醇喂养（10 天自由口服 Lieber-DeCarli 乙醇液体饮食）加单次 binge 乙醇喂养的简单酒精性肝损伤小鼠模型。这种慢性加单次 binge 乙醇喂养方案协同诱导肝损伤、炎症和脂肪肝，模拟了患者的慢性酒精性肝损伤急性发作。该喂养方案还可以延长至长达 8 周的慢性喂养加单次或多次 binge。慢性 binge 乙醇喂养导致高血液酒精水平；因此，这种简单的模型将非常有助于研究酒精性肝病 (ALD) 和其他由酒精摄入损害的器官。
