Shin Soo K, Kaiser Erin E, West Franklin D
Regenerative Bioscience Center, University of Georgia, Athens, GA, United States.
Interdisciplinary Toxicology Program, University of Georgia, Athens, GA, United States.
Front Physiol. 2021 Jan 7;11:592950. doi: 10.3389/fphys.2020.592950. eCollection 2020.
Alcohol is one of the most commonly abused intoxicants with 1 in 6 adults at risk for alcohol use disorder (AUD) in the United States. As such, animal models have been extensively investigated with rodent AUD models being the most widely studied. However, inherent anatomical and physiological differences between rodents and humans pose a number of limitations in studying the complex nature of human AUD. For example, rodents differ from humans in that rodents metabolize alcohol rapidly and do not innately demonstrate voluntary alcohol consumption. Comparatively, pigs exhibit similar patterns observed in human AUD including voluntary alcohol consumption and intoxication behaviors, which are instrumental in establishing a more representative AUD model that could in turn delineate the risk factors involved in the development of this disorder. Pigs and humans also share anatomical similarities in the two major target organs of alcohol- the brain and liver. Pigs possess gyrencephalic brains with comparable cerebral white matter volumes to humans, thus enabling more representative evaluations of susceptibility and neural tissue damage in response to AUD. Furthermore, similarities in the liver result in a comparable rate of alcohol elimination as humans, thus enabling a more accurate extrapolation of dosage and intoxication level to humans. A porcine model of AUD possesses great translational potential that can significantly advance our current understanding of the complex development and continuance of AUD in humans.
酒精是最常被滥用的致醉物之一,在美国,每6名成年人中就有1人有酒精使用障碍(AUD)的风险。因此,动物模型已被广泛研究,其中啮齿动物AUD模型是研究最为广泛的。然而,啮齿动物和人类在解剖学和生理学上的固有差异给研究人类AUD的复杂本质带来了一些限制。例如,啮齿动物与人类的不同之处在于,啮齿动物代谢酒精速度快,且天生不会表现出自愿饮酒行为。相比之下,猪表现出与人类AUD中观察到的类似模式,包括自愿饮酒和醉酒行为,这有助于建立一个更具代表性的AUD模型,进而阐明该疾病发展过程中的风险因素。猪和人类在酒精的两个主要靶器官——大脑和肝脏——也有解剖学上的相似之处。猪的大脑有脑回,其脑白质体积与人类相当,因此能够对AUD引起的易感性和神经组织损伤进行更具代表性的评估。此外,猪的肝脏与人类相似,酒精消除率相当,因此能够更准确地将剂量和中毒水平外推至人类。AUD的猪模型具有巨大的转化潜力,可显著推进我们目前对人类AUD复杂发展和持续情况的理解。