The extensive use of the broad-spectrum antibiotics like oxytetracycline (OTC) has become a serious environmental issue globally. OTC has profound negative effects on aquatic organisms including fishes. In this study, RNA-Seq analysis was employed to examine the possible molecular mechanism of hepatotoxicology in zebrafish induced by OTC exposure. Adult male zebrafish was exposed to 0, 5, 90, and 450 μg/L OTC for 3 weeks. The results showed the decrease in body weight and tail length but the increase in total length of zebrafish under OTC exposure in a dose-dependent way. In addition, severe histopathological damages were featured by increasing tissue vacuolization in the livers of 450 μg/L OTC group. Moreover, RNA-Seq analysis revealed that molecular signaling and functional pathways in the liver were disrupted by OTC exposure. Furthermore, the down-regulation of gene expression after OTC exposure was found on both the genes related to fatty acid degradation and the genes related to lipid synthesis. The present study implied that OTC induced liver malfunction and fish health risks through growth retard, histopathological damages, molecular signaling disruption, genetic expression alteration, and lipid metabolism disturbance.

土霉素（OTC）等广谱抗生素的广泛使用已成为全球严重的环境问题。OTC 对包括鱼类在内的水生生物具有深远的负面影响。在本研究中，采用 RNA-Seq 分析来检查 OTC 暴露诱导的斑马鱼肝毒理学可能的分子机制。成年雄性斑马鱼暴露于 0、5、90 和 450 μg/L OTC 3 周。结果表明，在 OTC 暴露下，斑马鱼的体重和尾长减少，但总长度增加，呈剂量依赖性。此外，450 μg/L OTC 组的肝脏组织空泡化增加，组织病理学损害严重。此外，RNA-Seq 分析显示，肝脏中的分子信号传导和功能通路被 OTC 暴露破坏。此外，在与脂肪酸降解相关的基因和与脂质合成相关的基因上都发现了OTC暴露后基因表达的下调。目前的研究表明，OTC 通过生长迟缓、组织病理学损伤、分子信号破坏、基因表达改变和脂质代谢紊乱引起肝功能障碍和鱼类健康风险。