Thioacetamide induced liver damage in zebrafish embryo as a disease model for steatohepatitis
Thioacetamide induced liver damage in zebrafish embryo as a disease model for steatohepatitis
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DOI：
10.1007/s11373-005-9055-5
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发表时间：
2006-03-01
影响因子：
11
通讯作者：
Wu, JL
中科院分区：
文献类型：
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作者：
Amali, AA;Rekha, RD;Wu, JL
脂肪性肝炎最近作为影响肝纤维化、肝硬化、腺瘤和肝癌进展的辅助因素而增加;然而，其导致肝损伤的机制仍不确定。我们使用硫代乙酰胺（TAA）在斑马鱼胚胎中诱导脂肪性肝炎。TUNEL法检测发现，受精后5d，肝脏细胞凋亡明显增加，凋亡基因bad、bax、P-38 a、caspase-3和8、JNK-1表达上调。油红O染色的组织切片显示脂肪滴的积聚，其导致核向一侧推动。还观察到脂肪变性标志物如ACC、脂联素、PTL、CEBP-α和β、SREBP-1的上调。此外，谷胱甘肽过氧化物酶在TAA处理的胚胎中的升高表明TAA诱导脂质过氧化，从而导致肝损伤。斑马鱼已经被认为是一种良好的人类疾病模型，在这种情况下，TAA处理的斑马鱼可以作为一个很好的动物模型来研究脂肪性肝炎的分子发病机制。此外，由于缺乏预防脂肪性肝炎的特异性药物，该动物模型可作为研究治疗策略和评估该疾病的化学预防策略的强大临床前平台。
Steatohepatitis has recently been increasing as a cofactor influencing the progression of fibrosis, cirrhosis, adenoma and carcinoma in liver; however, the mechanisms by which it contributes to liver injury remain uncertain. We induced steatohepatitis in zebrafish embryos using thioacetamide (TAA). TUNEL assay revealed significant increasing of apoptosis in liver after 5 days post fertilization and the increasing of apoptosis was observed to be associated with the up-regulation of apoptotic genes such as, bad, bax, P-38a, caspase-3 and 8, and JNK-1. Histological sections by oil red O stain showed the accumulation of fatty droplets which causes the pushing of the nucleus towards one side. Up-regulation of steatosis markers such as, ACC, adiponectin, PTL, CEBP-alpha and beta, SREBP-1 was also observed. Furthermore, the elevation of glutathione peroxidase in TAA treated embryos indicated that TAA induces lipid peroxidation which leads to causes liver damage. Zebrafish has already been considered as a good human disease model and in this context; TAA-treated zebrafish may serve as a good animal model to study the molecular pathogenesis of steatohepatitis. Moreover, non-availability of specific drugs to prevent steatohepatitis, this animal model may serve as a powerful preclinical platform to study the therapeutic strategies and for evaluating chemoprevention strategies for this disease.