中国药物警戒 ›› 2026, Vol. 23 ›› Issue (1): 19-25.
DOI: 10.19803/j.1672-8629.20250864

• 雷公藤效-毒研究专栏 • 上一篇    下一篇

基于多准则决策与斑马鱼模型实验的雷公藤多苷片治疗类风湿关节炎效益-风险研究

张晓朦1,2, 袁悦莹3,△, 季宇鑫1, 赵雪晶1, 林志健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;
    3北京中医药大学北京中医药研究院,北京 102488
  • 收稿日期:2025-11-30 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
  • 作者简介:张晓朦,女,博士,讲师,中药药物警戒与合理用药。△为并列第一作者。
  • 基金资助:
    国家自然科学基金资助项目（82204643）; 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）

Benefit-Risk Assessment of Tripterygium Glycosides Tablets in the Treatment of Rheumatoid Arthritis Based on an MCDA and Zebrafish Model

ZHANG Xiaomeng1,2, YUAN Yueying3,△, JI Yuxin1, ZHAO Xuejing1, LIN Zhijian1,2, ZHANG Bing1,2,*   

  1. 1School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China;
    2Center for Phamacovigilance and Rational Use of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China;
    3Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China
  • Received:2025-11-30 Online:2026-01-15 Published:2026-01-15

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摘要： 目的 量化评价雷公藤多苷片（Tripterygium Glycosides Tablets, TGT）治疗类风湿关节炎（Rheumatoid Arthritis, RA）的效益-风险,探索优化用药策略。方法 基于多准则决策（Multiple Critia Decision Analysis, MCDA）模型对纳入的随机对照试验（Random Clinical Trials,RCT）进行定量效益-风险评价,模拟不同用药条件对TGT效益-风险的影响。以斑马鱼为模型,采用响应面法模拟剂量、暴露时长、联合用药对风险的交互作用,筛选毒性最低的参数组合。结果 共纳入60项RCT,MCDA评价显示TGT治疗RA的效益大于风险。规定剂量（60~90 mg·d-1）、短疗程（<2个月）及联用甲氨蝶呤片（Metho Trexate, MTX）的情形下效益-风险结果更好。斑马鱼响应面分析表明,雷公藤甲素浓度为48.91 mg·L-1、暴露时长为48.39 h、MTX浓度为109.35 μmol·L-1时,斑马鱼心脏静脉窦-动脉球距离预测值最接近正常值1,提示毒性表达最低。该实验参数组合为临床策略提供了参考。结论 本研究结合临床评价与生物实验的研究范式,量化识别出“规定剂量、短疗程、联合MTX”为TGT治疗RA的优化策略,为其精准应用提供了量化依据与科学基础。

关键词: 雷公藤多苷片, 类风湿关节炎, 效益-风险评价, 多准则决策, 斑马鱼, 响应面分析

Abstract: Objective To quantitatively evaluate the benefits and risks of Tripterygium Glycosides tablets (TGT) in the treatment of rheumatoid arthritis (RA) and to explore optimized medications. Methods A multi-criteria decision analysis (MCDA) model was used for a quantitative benefit-risk assessment (BRA) of the included randomized controlled trials (RCTs) before the effects of varied medication conditions on the overall benefit-risk profiles of TGT were simulated. Using zebrafish as an in vivo model, the response surface methodology (RSM) was employed to analyze the interactions of dosage, exposure durations, and combination therapies with drug-related risks. The parameter with the lowest toxicity was screened. Results A total of 60 RCTs were included in the analysis. MCDA results suggested that the therapeutic benefits of TGT against RA outweighed risks. The results of BRAs were the best when the prescribed dosage ranged from 60 to 90 mg·d-1, the course of treatment was short (less than 2 months), and TGTs were combined with methotrexate (MTX). Zebrafish-based RSM analysis revealed that a triptolide concentration of 48.91 mg·L-1, an exposure duration of 48.39 hours, and an MTX concentration of 109.35 μmol·L-1 yielded a predicted SV-BA distance that was the closest to the reference value 1, indicating the minimal toxicity expressions.This optimal parameter set provided evidence for the clinically BRA derived strategies. Conclusion By combining clinical evaluation with biological experiments, this study has quantitatively identified “the prescribed dose, a short course of treatment, and combination with MTX” as the optimized usage of TGT against RA.

Key words: Tripterygium Glycosides Tablets, Rheumatoid Arthritis, Benefit-Risk Assessment, Multi-Criteria Decision Analysis, Zebrafish, Response Surface Methodology

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