Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
Methods Mol Biol. 2020;2164:145-157. doi: 10.1007/978-1-0716-0704-6_15.
Alcoholic liver disease (ALD) is one of the most common causes of chronic liver disease in Western countries. The spectrum of ALD ranges from simple steatosis to steatohepatitis to cirrhosis and hepatocellular carcinoma. Over the past 50 years, several animal models of ALD have been developed. Although none of them faithfully recapitulates the human disease, they have proven to be invaluable tools to study the pathogenesis of ALD, to identify potential therapeutic targets and to test new drugs. Here, we describe the mouse model of chronic and binge ethanol feeding, also known as the NIAAA model or Gao binge model. This model combines chronic feeding of Lieber-DeCarli ethanol liquid diet with acute administration of high-dose ethanol by oral gavage to mimic the drinking patterns of many alcoholic patients who engage in episodes of binge drinking on top of chronic daily drinking. Short-term (10-day) chronic plus single binge ethanol feeding causes a substantial increase in serum transaminase levels, moderate steatosis and mild inflammation characterized by lobular neutrophil infiltration. Long-term (8-week) chronic plus single or multiple (twice a week) binge ethanol feeding induce more severe steatohepatitis and mild fibrosis. This clinically relevant, easy-to-perform model of ALD is currently used by many research laboratories to reproduce early stages of human alcoholic steatohepatitis.
酒精性肝病(ALD)是西方国家最常见的慢性肝病病因之一。ALD 的范围从单纯脂肪变性到脂肪性肝炎、肝硬化和肝细胞癌。在过去的 50 年中,已经开发出几种 ALD 的动物模型。尽管它们都不能忠实地再现人类疾病,但它们已被证明是研究 ALD 发病机制、确定潜在治疗靶点和测试新药的宝贵工具。在这里,我们描述了慢性和 binge 乙醇喂养的小鼠模型,也称为 NIAAA 模型或 Gao binge 模型。该模型将 Lieber-DeCarli 乙醇液体饮食的慢性喂养与口服大剂量乙醇的急性给予相结合,以模拟许多酗酒患者的饮酒模式,他们在慢性每日饮酒的基础上进行 binge 饮酒。短期(10 天)慢性加单次 binge 乙醇喂养会导致血清转氨酶水平显著升高、中度脂肪变性和以小叶中性粒细胞浸润为特征的轻度炎症。长期(8 周)慢性加单次或多次(每周两次) binge 乙醇喂养会引起更严重的脂肪性肝炎和轻度纤维化。这种具有临床相关性、易于实施的 ALD 模型目前被许多研究实验室用于复制人类酒精性脂肪性肝炎的早期阶段。