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急性酒精性肝炎的小鼠模型及其与人类疾病的相关性。

Murine Models of Acute Alcoholic Hepatitis and Their Relevance to Human Disease.

作者信息

Wilkin Richard J W, Lalor Patricia F, Parker Richard, Newsome Philip N

机构信息

National Institute for Health Research Birmingham Liver Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, United Kingdom; Liver Unit, University Hospital Birmingham NHS Foundation Trust, Birmingham, United Kingdom.

National Institute for Health Research Birmingham Liver Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, United Kingdom; Liver Unit, University Hospital Birmingham NHS Foundation Trust, Birmingham, United Kingdom.

出版信息

Am J Pathol. 2016 Apr;186(4):748-60. doi: 10.1016/j.ajpath.2015.12.003. Epub 2016 Feb 1.

Abstract

Alcohol-induced liver damage is a major burden for most societies, and murine studies can provide a means to better understand its pathogenesis and test new therapies. However, there are many models reported with widely differing phenotypes, not all of which fully regenerate the spectrum of human disease. Thus, it is important to understand the implications of these variations to efficiently model human disease. This review critically appraises key articles in the field, detailing the spectrum of liver damage seen in different models, and how they relate to the phenotype of disease seen in patients. A range of different methods of alcohol administration have been studied, ranging from ad libitum consumption of alcohol and water to modified diets (eg, Lieber deCarli liquid diet). Other feeding regimens have taken more invasive routes using intragastric feeding tubes to infuse alcohol directly into the stomach. Notably, models using wild-type mice generally produce a milder phenotype of liver damage than those using genetically modified mice, with the exception of the chronic binge-feeding model. We recommend panels of tests for consideration to standardize end points for the evaluation of the severity of liver damage-key for comparison of models of injury, testing of new therapies, and subsequent translation of findings into clinical practice.

摘要

酒精性肝损伤是大多数社会面临的一项主要负担,而小鼠研究能够提供一种手段,以更好地理解其发病机制并测试新的疗法。然而,目前报道了许多模型,其表型差异很大,并非所有模型都能完全重现人类疾病的全貌。因此,了解这些差异的影响对于有效模拟人类疾病很重要。这篇综述批判性地评估了该领域的关键文章,详细阐述了在不同模型中观察到的肝损伤范围,以及它们与患者疾病表型的关系。人们研究了一系列不同的酒精给药方法,从随意饮用酒精和水到改良饮食(如Lieber deCarli液体饮食)。其他喂养方案则采用了更具侵入性的途径,使用胃内喂养管将酒精直接注入胃中。值得注意的是,除了慢性暴饮模型外,使用野生型小鼠的模型通常比使用基因改造小鼠的模型产生的肝损伤表型更轻。我们建议考虑采用一组测试来标准化评估肝损伤严重程度的终点——这对于比较损伤模型、测试新疗法以及随后将研究结果转化为临床实践至关重要。

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