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、1000μg·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。
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(10μmol·L^(-1)),hyperuricemia(100μmol·L^(-1))+DOX(10μmol·L^(-1)),allopurinol(136μg·mL^(-1))+DOX(10μmol·L^(-1)),hyperuricemia(100μmol·L^(-1))+DOX(10μmol·L^(-1))+ferroptosis inhibitor Fer-1(1μmol·L^(-1)),and hyperuricemia(100μmol·L^(-1))+DOX(10μmol·L^(-1))+chicory extract(low/high dose:500/1000μg·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.
作者
蔡海丽
张晓朦
刘亚迪
陈莉娟
王雨
张冰
CAI Haili;ZHANG Xiaomeng;LIU Yadi;CHEN Lijuan;WANG Yu;ZHANG Bing(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China;Center for Pharmacovigilance and Rational Use of Chinese Medicine,Beijing University of Chinese Medicine,Beijing 102488,China)
出处
《中国药物警戒》
2025年第8期876-882,共7页
Chinese Journal of Pharmacovigilance
基金
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)。
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
Ferroptosis
Anthracyclins(ANTs)
Cardiotoxicity
Hyperuricemia
Zebrafish
Pharmacovigilance
作者简介
蔡海丽,女,硕士,中药药物警戒与合理用药;通信作者: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。
