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慢性和 binge 乙醇喂养的小鼠模型(NIAAA 模型)。

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

机构信息

Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism NIAAA, National Institutes of Health NIH, Bethesda, Maryland, USA.

出版信息

Nat Protoc. 2013 Mar;8(3):627-37. doi: 10.1038/nprot.2013.032. Epub 2013 Feb 28.

Abstract

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.

摘要

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。

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