中国药物警戒 ›› 2025, Vol. 22 ›› Issue (8): 876-882.
DOI: 10.19803/j.1672-8629.20250310

• 药源性心脏毒性预警研究专栏（一） • 上一篇    下一篇

基于铁死亡探讨中药防治蒽环类药物心脏毒性的机制

蔡海丽1, 张晓朦1,2, 刘亚迪1, 陈莉娟1, 王雨1,2, 张冰1,2*   

  1. 1北京中医药大学中药学院,北京 102488;
    2北京中医药大学中药药物警戒与合理用药研究中心,北京 102488
  • 收稿日期:2025-05-15 出版日期:2025-08-15 发布日期:2025-08-13
  • 通讯作者: *张冰,女,博士,教授·博导,中药药物警戒与合理用药。E-mail: zhangb@bucm.edu.cn
  • 作者简介:蔡海丽,女,硕士,中药药物警戒与合理用药。
  • 基金资助:
    国家自然科学基金资助项目（82274117、82204643）; 中央高校基本科研业务费揭榜挂帅项目（2024-JYB-JBZD-054）

Preventive Strategies for Anthracycline-Induced Cardiotoxicity Using Traditional Chinese Medicine via Ferroptosis Regulation

CAI Haili1, ZHANG Xiaomeng1,2, LIU Yadi1, CHEN Lijuan1, WANG Yu1,2, ZHANG Bing1,2*   

  1. 1School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China;
    2Center for Pharmacovigilance and Rational Use of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China
  • Received:2025-05-15 Online:2025-08-15 Published:2025-08-13

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摘要： 目的 探讨蒽环类药物心脏毒性中高水平尿酸-铁死亡路径的作用,评价中药菊苣提取物的干预效果。方法 采用3 dpf斑马鱼仔鱼建立阿霉素诱导的心脏毒性模型,设置对照组、阿霉素（10μmol·L-1）组、高尿酸（100μmol·L-1）+阿霉素（10μmol·L-1）组、别嘌醇（136μg·mL-1）+阿霉素（10μmol·L-1）组、高尿酸（100μmol·L-1）+阿霉素（10μmol·L-1）+铁死亡抑制剂Fer-1（1μmol·L-1）组和高尿酸+阿霉素+低、高剂量菊苣提取物组（500、1 000μg·mL-1）,检测生存率、心率和心脏形态学指标（SV-BA间距、心包水肿）。结果 高水平尿酸显著加重阿霉素诱导的心脏毒性,表现为心率加快、SV-BA距离增加及心包水肿加重（P<0.05或P<0.01）;铁死亡抑制剂Fer-1和菊苣提取物均可显著改善上述心脏损伤（P<0.01）,且菊苣高剂量组效果更优。结论 高水平尿酸可能通过激活铁死亡路径加剧蒽环类药物心脏毒性,中药菊苣提取物能发挥心脏保护作用,监测铁死亡相关生物标志物可建立有效的毒性预警体系,为临床用药提供参考。

关键词: 铁死亡, 蒽环类药物, 心脏毒性, 高尿酸, 斑马鱼, 药物警戒

Abstract: Objective To investigate the role of the hyperuricemia-ferroptosis pathway in anthracycline-induced cardiotoxicity and evaluate the effects of intervention of chicory (Cichorium intybus L.) extract, a traditional Chinese medicine. Methods A doxorubicin (DOX)-induced cardiotoxicity model was established using zebrafish larvae at 3 days post-fertilization (dpf). The larvae were divided into seven groups: control, DOX alone (10 μmol·L-1), hyperuricemia (100 μmol·L-1) + DOX(10 μmol·L-1), allopurinol (136 μg·mL-1) + DOX(10 μmol·L-1), hyperuricemia(100 μmol·L-1) + DOX(10 μmol·L-1) +ferroptosis inhibitor Fer-1 (1 μmol·L-1), and hyperuricemia(100 μmol·L-1) + DOX(10 μmol·L-1) + chicory extract (low/high dose: 500/1 000 μg·mL-1). Survival rate, heart rate, and cardiac morphological parameters (SV-BA distance and pericardial edema) were recorded. Results Hyperuricemia significantly exacerbated DOX-induced cardiotoxicity, which was manifested as increased heart rate, extended SV-BA distance, and aggravated pericardial edema (P<0.05 or P<0.01). Both Fer-1 and chicory extract markedly ameliorated cardiac injury (P<0.01), especially in the high-dose chicory group. Conclusion Hyperuricemia may aggravate anthracycline cardiotoxicity by activating ferroptosis, while the chicory extract exerts cardioprotective effects. Monitoring ferroptosis-related biomarkers could help establish an early warning system and provide novel strategies for clinical prevention and treatment.

Key words: Ferroptosis, Anthracyclins(ANTs), Cardiotoxicity, Hyperuricemia, Zebrafish, Pharmacovigilance

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