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酒精性肝病:动物模型的应用。

Alcoholic liver disease: Utility of animal models.

机构信息

Department of Immunology, Ophthalmology and ORL, Complutense University School of Medicine, Madrid 28040, Spain.

Institute for Bioengineering (IBioE), School of Engineering, Faraday Building, The University of Edinburgh, Edinburgh EH9 3 JL, Scotland, United Kingdom.

出版信息

World J Gastroenterol. 2018 Dec 7;24(45):5063-5075. doi: 10.3748/wjg.v24.i45.5063.

Abstract

Alcoholic liver disease (ALD) is a major cause of acute and chronic liver injury. Extensive evidence has been accumulated on the pathological process of ALD during the past decades. However, effective treatment options for ALD are very limited due to the lack of suitable models that recapitulate the full spectrum of ALD. Experimental animal models of ALD, particularly rodents, have been used extensively to mimic human ALD. An ideal animal model should recapitulate all aspects of the ALD process, including significant steatosis, hepatic neutrophil infiltration, and liver injury. A better strategy against ALD depends on clear diagnostic biomarkers, accurate predictor(s) of its progression and new therapeutic approaches to modulate stop or even reverse the disease. Numerous models employing rodent animals have been established in the last decades to investigate the effects of acute and chronic alcohol exposure on the initiation and progression of ALD. Although significant progress has been made in gaining better knowledge on the mechanisms and pathology of ALD, many features of ALD are unknown, and require further investigation, ideally with improved animal models that more effectively mimic human ALD. Although differences in the degree and stages of alcoholic liver injury inevitably exist between animal models and human ALD, the acquisition and translational relevance will be greatly enhanced with the development of new and improved animal models of ALD.

摘要

酒精性肝病 (ALD) 是急性和慢性肝损伤的主要原因。在过去几十年中,已经积累了大量关于 ALD 病理过程的证据。然而,由于缺乏能够重现 ALD 全貌的合适模型,ALD 的有效治疗选择非常有限。ALD 的实验动物模型,特别是啮齿动物,已被广泛用于模拟人类 ALD。理想的动物模型应该能够重现 ALD 过程的各个方面,包括明显的脂肪变性、肝中性粒细胞浸润和肝损伤。更好的 ALD 防治策略取决于明确的诊断生物标志物、疾病进展的准确预测因子以及调节疾病进展的新治疗方法。在过去的几十年中,已经建立了许多使用啮齿动物的模型来研究急性和慢性酒精暴露对 ALD 的起始和进展的影响。尽管在获得关于 ALD 机制和病理学的更好知识方面已经取得了重大进展,但 ALD 的许多特征仍不清楚,需要进一步研究,理想情况下是使用更有效地模拟人类 ALD 的改进动物模型。尽管动物模型和人类 ALD 之间不可避免地存在酒精性肝损伤程度和阶段的差异,但随着新的和改进的 ALD 动物模型的发展,将极大地增强获得和转化的相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15c0/6288648/aa3a6edf36c1/WJG-24-5063-g001.jpg

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