Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Biomolecules. 2018 Jan 13;8(1):3. doi: 10.3390/biom8010003.
Both chronic and acute (binge) alcohol drinking are important health and economic concerns worldwide and prominent risk factors for the development of alcoholic liver disease (ALD). There are no FDA-approved medications to prevent or to treat any stage of ALD. Therefore, discovery of novel therapeutic strategies remains a critical need for patients with ALD. Relevant experimental animal models that simulate human drinking patterns and mimic the spectrum and severity of alcohol-induced liver pathology in humans are critical to our ability to identify new mechanisms and therapeutic targets. There are several animal models currently in use, including the most widely utilized chronic ad libitum ethanol (EtOH) feeding (Lieber-DeCarli liquid diet model), chronic intragastric EtOH administration (Tsukamoto-French model), and chronic-plus-binge EtOH challenge (Bin Gao-National Institute on Alcohol Abuse and Alcoholism (NIAAA) model). This review provides an overview of recent advances in rodent models of binge EtOH administration which help to recapitulate different features and etiologies of progressive ALD. These models include EtOH binge alone, and EtOH binge coupled with chronic EtOH intake, a high fat diet, or endotoxin challenge. We analyze the strengths, limitations, and translational relevance of these models, as well as summarize the liver injury outcomes and mechanistic insights. We further discuss the application(s) of binge EtOH models in examining alcohol-induced multi-organ pathology, sex- and age-related differences, as well as circadian rhythm disruption.
慢性和急性（ binge ）饮酒都是全球重要的健康和经济问题，也是导致酒精性肝病（ ALD ）的主要危险因素。目前还没有获得 FDA 批准的药物可用于预防或治疗 ALD 的任何阶段。因此，发现新的治疗策略仍然是 ALD 患者的迫切需求。相关的实验动物模型可以模拟人类的饮酒模式，并模拟人类酒精引起的肝脏病理学的范围和严重程度，这对于我们识别新的机制和治疗靶点至关重要。目前有几种动物模型正在使用，包括最广泛使用的慢性随意乙醇（ EtOH ）喂养（ Lieber-DeCarli 液体饮食模型）、慢性胃内 EtOH 给药（ Tsukamoto-French 模型）和慢性加 binge EtOH 挑战（ Bin Gao-National Institute on Alcohol Abuse and Alcoholism （ NIAAA ）模型）。这篇综述概述了 binge EtOH 给药的啮齿动物模型的最新进展，这些模型有助于再现进行性 ALD 的不同特征和病因。这些模型包括单独的 EtOH binge ，以及 EtOH binge 与慢性 EtOH 摄入、高脂肪饮食或内毒素挑战相结合。我们分析了这些模型的优势、局限性和转化相关性，以及总结了肝损伤的结果和机制见解。我们进一步讨论了 binge EtOH 模型在检查酒精引起的多器官病理学、性别和年龄相关差异以及昼夜节律紊乱中的应用。
