Department of Medicine II, Section Molecular Hepatology-Alcohol Associated Diseases, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Am J Physiol Gastrointest Liver Physiol. 2013 Mar 1;304(5):G449-68. doi: 10.1152/ajpgi.00199.2012. Epub 2012 Dec 28.
Chronic liver diseases are frequent and potentially life threatening for humans. The underlying etiologies are diverse, ranging from viral infections, autoimmune disorders, and intoxications (including alcohol abuse) to imbalanced diets. Although at early stages of disease the liver regenerates in the absence of the insult, advanced stages cannot be healed and may require organ transplantation. A better understanding of underlying mechanisms is mandatory for the design of new drugs to be used in clinic. Therefore, rodent models are being developed to mimic human liver disease. However, no model to date can completely recapitulate the "corresponding" human disorder. Limiting factors are the time frame required in humans to establish a certain liver disease and the fact that rodents possess a distinct immune system compared with humans and have different metabolic rates affecting liver homeostasis. These features account for the difficulties in developing adequate rodent models for studying disease progression and for testing new pharmaceuticals to be translated into the clinic. Nevertheless, traditional and new promising animal models that mimic certain attributes of chronic liver diseases are established and being used to deepen our understanding in the underlying mechanisms of distinct liver diseases. This review aims at providing a comprehensive overview of recent advances in animal models recapitulating different features and etiologies of human liver diseases.
慢性肝脏疾病在人类中较为常见,并且可能危及生命。其潜在病因多种多样,包括病毒感染、自身免疫性疾病和中毒(包括酗酒)以及饮食失衡等。尽管在疾病的早期阶段,肝脏在没有损伤的情况下会进行再生,但在晚期阶段,肝脏无法被治愈,可能需要进行器官移植。为了设计新的药物并应用于临床,我们必须深入了解潜在的发病机制。因此,人们开发了啮齿动物模型来模拟人类肝脏疾病。然而,迄今为止,没有一种模型可以完全再现“相应的”人类疾病。其限制因素是人类建立特定肝脏疾病所需的时间框架,以及啮齿动物与人类的免疫系统明显不同,并且具有不同的代谢率,从而影响肝脏的内稳态。这些特征导致开发用于研究疾病进展和测试新药物以转化为临床应用的合适啮齿动物模型存在困难。尽管如此,仍建立了传统和新的有前景的动物模型来模拟慢性肝脏疾病的某些特征,并用于加深我们对不同肝脏疾病潜在发病机制的理解。本综述旨在全面概述重现人类肝脏疾病不同特征和病因的新型动物模型的最新进展。