Lin Jiun-Nong, Chang Lin-Li, Lai Chung-Hsu, Lin Kai-Jen, Lin Mei-Fang, Yang Chih-Hui, Lin Hsi-Hsun, Chen Yen-Hsu
1 Department of Critical Care Medicine, E-Da Hospital, I-Shou University , Kaohsiung, Taiwan .
2 School of Medicine, College of Medicine, I-Shou University , Kaohsiung, Taiwan .
Zebrafish. 2015 Aug;12(4):271-80. doi: 10.1089/zeb.2014.1054. Epub 2015 Apr 29.
Alcoholic liver disease (ALD) continues to be a major cause of liver-related morbidity and mortality worldwide. To date, no zebrafish animal model has demonstrated the characteristic manifestations of ALD in the setting of chronic alcohol exposure. The aim of this study was to develop a zebrafish animal model for ALD. Male adult zebrafish were housed in a 1% (v/v) ethanol solution up to 3 months. A histopathological study showed the characteristic features of alcoholic liver steatosis and steatohepatitis in the early stages of alcohol exposure, including fat droplet accumulation, ballooning degeneration of the hepatocytes, and Mallory body formation. As the exposure time increased, collagen deposition in the extracellular matrix was observed by Sirius red staining and immunofluorescence staining. Finally, anaplastic hepatocytes with pleomorphic nuclei were arranged in trabecular patterns and formed nodules in the zebrafish liver. Over the time course of 1% ethanol exposure, upregulations of lipogenesis, fibrosis, and tumor-related genes were also revealed by semiquantitative and quantitative real-time reverse transcription-polymerase chain reaction. As these data reflect characteristic liver damage by alcohol in humans, this zebrafish animal model may serve as a powerful tool to study the pathogenesis and treatment of ALD and its related disorders in humans.
酒精性肝病（ALD）仍然是全球范围内肝脏相关发病和死亡的主要原因。迄今为止，尚无斑马鱼动物模型能在慢性酒精暴露情况下展现出ALD的特征性表现。本研究的目的是建立一种用于ALD的斑马鱼动物模型。成年雄性斑马鱼饲养在1%（v/v）乙醇溶液中长达3个月。组织病理学研究显示，在酒精暴露早期出现酒精性肝脂肪变性和脂肪性肝炎的特征性表现，包括脂滴积聚、肝细胞气球样变性和马洛里小体形成。随着暴露时间增加，通过天狼星红染色和免疫荧光染色观察到细胞外基质中的胶原沉积。最后，具有多形核的间变肝细胞呈小梁状排列，并在斑马鱼肝脏中形成结节。在1%乙醇暴露的时间进程中，半定量和定量实时逆转录-聚合酶链反应也显示了脂肪生成、纤维化和肿瘤相关基因的上调。由于这些数据反映了酒精对人类肝脏的特征性损伤，这种斑马鱼动物模型可能成为研究人类ALD及其相关疾病的发病机制和治疗方法的有力工具。
