Department of Surgery, Carolinas Medical Center, 1000 Blythe Boulevard, Charlotte, NC 28203, USA.
Alcohol. 2012 Dec;46(8):715-25. doi: 10.1016/j.alcohol.2012.08.004. Epub 2012 Sep 7.
Alcoholic liver disease (ALD) is a major cause of acute and chronic liver disease worldwide. The progressive nature of ALD is well described; however, the complex interactions under which these pathologies evolve remain to be fully elucidated. Clinically there are no clear biomarkers or universally accepted, effective treatment strategies for ALD. Experimental models of ALD are an important component in identifying underlying mechanisms of alcohol-induced injury to develop better diagnostic markers, predictors of disease progression, and therapeutic targets to manage, halt, or reverse disease progression. Rodents remain the most accessible model for studying ALD pathology. Effective rodent models must mimic the natural history of ALD while allowing examination of complex interactions between multiple hepatic, and non-hepatic, cell types in the setting of altered metabolic or oxidative/nitrosative stress, inflammatory responses, and sensitivity to cytotoxic stress. Additionally, mode and duration of alcohol delivery influence hepatic response and present unique challenges in understanding disease pathology. This review provides an overview of rodent models of ALD, their strengths and weaknesses relative to human disease states, and provides insight of the potential to develop novel rodent models to simulate the course of human ALD.
酒精性肝病(ALD)是全球急性和慢性肝病的主要原因。ALD 的进展性质已有很好的描述;然而,这些病变演变的复杂相互作用仍有待充分阐明。临床上,ALD 没有明确的生物标志物或普遍接受的有效治疗策略。ALD 的实验模型是确定酒精引起损伤的潜在机制的重要组成部分,以开发更好的诊断标志物、疾病进展预测因子以及治疗靶点,以管理、阻止或逆转疾病进展。啮齿动物仍然是研究 ALD 病理学的最易接近的模型。有效的啮齿动物模型必须模拟 ALD 的自然史,同时允许在改变的代谢或氧化/硝化应激、炎症反应以及对细胞毒性应激的敏感性的情况下,检查多个肝和非肝细胞类型之间的复杂相互作用。此外,酒精输送的方式和持续时间会影响肝脏的反应,并在理解疾病病理学方面带来独特的挑战。本综述概述了 ALD 的啮齿动物模型,及其相对于人类疾病状态的优缺点,并提供了开发模拟人类 ALD 过程的新型啮齿动物模型的潜力的见解。