中国药物警戒 ›› 2026, Vol. 23 ›› Issue (1): 12-18.
DOI: 10.19803/j.1672-8629.20250634

• 雷公藤效-毒研究专栏 • 上一篇    下一篇

基于计算预测与斑马鱼观察雷公藤甲素治疗系统性红斑狼疮的效-毒研究

季宇鑫1, 林彦1, 冯鑫煜1, 王雨1,2, 张晓朦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:2025-09-07 出版日期:2026-01-15 发布日期:2026-01-15
  • 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; #为共同通信作者。
  • 作者简介:季宇鑫,男,在读硕士,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（82204643、82274117）; 国家中医药管理局高水平重点学科建设项目-临床中药学（zyyzdxk-2023257）

Efficacy-Toxicity of Triptolide in Treating Systemic Lupus Erythematosus: Computational Prediction and Zebrafish Observations

JI Yuxin1, LIN Yan1, FENG Xinyu1, WANG Yu1,2, ZHANG Xiaomeng1,2#, 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:2025-09-07 Online:2026-01-15 Published:2026-01-15

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摘要： 目的 探讨雷公藤甲素（Triptolide, TP）器官毒性发生与时序规律、剂量蓄积的关系,初步分析其疗效-毒性机制,为提高TP临床使用安全性提供参考。方法 以2 dpf斑马鱼胚胎为模型,设置荧光标记TP暴露组,于72 h后动态观察心脏、肝脏、肾脏及胃肠道毒性出现顺序及相关表型改变;利用网络药理学与网络毒理学筛选TP治疗系统性红斑狼疮及器官毒性共同靶点,进行GO/KEGG富集分析。结果 TP可依次诱发斑马鱼肝脏（72 h）、心脏（74 h）、胃肠道（78 h）及肾脏（80 h）损伤;富集分析提示其“效-毒”机制高度相似,其潜在分子机制与凋亡、炎症反应等通路相关,白蛋白或为TP器官毒性标志指标。结论 TP所致器官毒性呈现明显时序性与剂量依赖性,其“效-毒”潜在机制高度相似提示其疗效与毒性关系可能与剂量蓄积有关,其结果可为临床时序性毒性监测与干预提供参考,为临床防治提供新策略。但斑马鱼在药物代谢以及结构与人类存在差异,其器官毒性顺序需结合临床案例研究补充。

关键词: 雷公藤甲素, 器官毒性, 时序规律, 分子机制, 斑马鱼, 中药药物警戒

Abstract: Objective To investigate the temporal sequence of development of organ toxicity induced by triptolide (TP) and its relationship with the cumulative dose, and analyze its efficacy-toxicity mechanisms in order to provide data on clinical safety of TP. Methods Using zebrafish embryos at 2 days post-fertilization (dpf) as a model, a fluorescently labeled TP exposure group was set up to dynamically observe the onset sequence of toxicity and related phenotypic alterations in the heart, liver, kidney and intestines 72 hours later. Network pharmacology and toxicology were used to identify common targets of TP in treating systemic lupus erythematosus and inducing organ toxicity before GO/KEGG enrichment analysis was conducted. Results Triptolide sequentially induced damage to the zebrafish liver (72 h), heart (74 h), intestines (78 h), and kidney (80 h). Enrichment analysis revealed that the potential mechanisms underlying its efficacy and toxicity were highly similar, involving molecular pathways related to apoptosis and inflammatory responses. ALB might serve as a potential biomarker for TP-induced organ toxicity. Conclusion The organ toxicity induced by TP is distinctly temporal and dose-dependent. The strong similarity in its potential “efficacy-toxicity” mechanisms suggests that the relationship between the therapeutic effect and toxicity may be associated with the cumulative dose. These findings can provide a reference for clinical oversight of and interventions in time-dependent toxicity, offering new strategies for clinical prevention and treatment. However, differences in drug metabolism and anatomical structure between zebrafish and humans require that the sequence of organ toxicity be studied based on clinical cases.

Key words: Triptolide, Organ Toxicity, Temporal Regularity, Molecular Mechanisms, Zebrafish, Pharmacovigilance of Traditional Chinese Medicine

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