| 张雨婷,刘鹏瑞,罗 琳,等.海洋天然产物普那布林在斑马鱼胚胎中的毒性效应研究[J].中国海洋药物,2026,(6):-. |
| 海洋天然产物普那布林在斑马鱼胚胎中的毒性效应研究 |
| Toxicological Evaluation of Marine-Derived Plinabulin in Zebrafish Embryos |
| 投稿时间：2025-03-30 修订日期：2025-06-27 |
| DOI： |
| 中文关键词: 普那布林 斑马鱼 毒性模型 心脏损伤 |
| English Keywords:Plinabulin, Zebrafish, Toxicity model, Cardiac injury |
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| 中文摘要: |
| 目的 普那布林（Plinabulin）是一种基于海洋天然产物开发的新型抗肿瘤药物，其作用机制主要涉及靶向癌细胞微管系统，目前正处于非小细胞肺癌治疗的III期临床实验阶段。然而，Plinabulin的高毒性限制了其临床应用，因此系统评估其在体内的毒性效应具有重要意义。方法 该研究通过建立斑马鱼胚胎毒性检测模型，包括急性毒性实验、胚胎暴露实验、毒理学分析及吖啶橙染色，以探究Plinabulin的潜在毒性作用。结果 Plinabulin暴露24 h后，斑马鱼胚胎的半数致死浓度（LC50）为100 nmol/L。胚胎暴露分析显示，尽管Plinabulin对斑马鱼胚胎的破膜率、幼鱼体长及耳石发育均无显著影响，但其可诱导心包水肿并显著提高心率。进一步的机制研究表明，Plinabulin可能通过促进细胞凋亡途径导致心脏损伤。结论 该研究阐明了Plinabulin通过细胞凋亡途径促使斑马鱼心脏损伤的毒性作用，为其临床安全性评估提供了重要的体内实验依据。 |
| English Summary: |
| Objective Plinabulin, a novel antitumor agent derived from marine natural products, primarily exerts its therapeutic effects by targeting the microtubule system of cancer cells. It is currently undergoing Phase III clinical trials for the treatment of non-small cell lung cancer. However, its high toxicity limits clinical application, necessitating a systematic evaluation of its in vivo toxicological effects. Methods The study established a zebrafish embryo toxicity assessment model, including acute toxicity tests, embryo exposure experiments, toxicological analyses, and acridine orange staining, to investigate the potential toxic effects of Plinabulin. Results Experimental results demonstrated that the median lethal concentration (LC50) of Plinabulin in zebrafish embryos after 24 hour exposure was 100 nmol/L. Embryo exposure analysis revealed that while Plinabulin did not significantly affect hatching rate, larval body length, or otolith development, it induced pericardial edema and significantly increased heart rate. Further mechanistic studies suggested that Plinabulin may contribute to cardiac injury by promoting apoptotic pathways. Conclusion This study demonstrates that Plinabulin induces cardiac toxicity in zebrafish via the apoptotic pathway, providing critical in vivo evidence for its clinical safety assessment. |
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