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胰腺疾病治疗药物联合应用协同作用的评价方法与策略
DOI: 10.12449/JCH260635
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Evaluation methods and strategies for the synergistic effect of drug combinations in pancreatic diseases
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摘要: 胰腺疾病具有诊治困难、作用机制复杂等特征。多药联用通过协同作用可实现增强药效、逆转耐药以及减少不良反应，已成为改善胰腺疾病治疗的重要策略。本综述系统归纳了目前常用的药物联用协同作用评价方法，包括等效线图解法、Chou-Talalay法、金正均法及权重配方法，详细阐述了其理论基础、适用范围与局限性，并总结其在胰腺癌与急性胰腺炎等疾病中的应用进展。通过比较不同方法在测量精度及实验依赖性方面的特点，构建了面向胰腺疾病的多药联用效应评价框架，为联合用药方案的筛选与优化提供依据，并为未来协同评价模型的创新与联合治疗策略的开发提供思路。Abstract: Pancreatic diseases are characterized by difficulties in diagnosis and treatment， as well as complex pathogenic mechanisms. Combined drug therapy can enhance therapeutic efficacy， overcome drug resistance， and reduce adverse effects through synergistic interactions and has thus emerged as an important strategy for improving the treatment of pancreatic diseases. This article systematically reviews the commonly used methods for evaluating the synergistic effect of drug combinations， including isobologram analysis， the Chou-Talalay method， Jin’s formula， and the weighted sum method， as well as the theoretical basis， applicability， and limitations of each method， and this article also summarizes the recent advances in their application in pancreatic diseases including pancreatic cancer and acute pancreatitis. By comparing the characteristics of different methods in terms of measurement accuracy and experimental dependence， this article further proposes a framework for evaluating the effect of multi-drug combinations tailored to pancreatic diseases， thereby providing a basis for the screening and optimization of drug combination regimens， as well as new perspectives for the future development of synergistic evaluation models and combined therapeutic strategies.
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Key words:
- Pancreatic Diseases /
- Drug Synergism /
- Drug Evaluation
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表 1 胰腺疾病中应用多药联合协同作用评价方法的比较
Table 1. Comparison of assessment methods for synergistic effects of drug combinations in pancreatic diseases
评价方法 核心假设 胰腺疾病中特异性
偏倚来源局限性 改进策略 最适研究阶段 Chou-
Talalay法基于质量作用定
律与剂量-效应
曲线药物渗透不均→曲线
斜率/IC50不稳定低/高效应区的协同
判断过于敏感增加实验剂量点；引入
3D类器官等高维模型；
结合算法模型进行参数
不确定性评估体外精确验证 等效线
图解法剂量等效原则 效应跨区间波动→等
效点偏移依赖单一等效点，易
受效应阈值波动影
响；剂量点稀疏→可
靠性受限绘制多个效应区间（20%/
50%/70%）进行交叉验证体外初筛+3D交叉
验证金正均法 概率相加 无法识别剂量-效应非
线性不能辨别剂量窗口
（如“中剂量协同、低
剂量无效”）的动态
协同现象结合体外CI/等效线结果
校正有效剂量动物/患者来源异种移
植模型、体内验证权重配方法 基于药物贡献度
加权受预设剂量范围与组
合矩阵限制主观性强、依赖机制
信息引入多组学/机制网络数
据定量权重机制研究、配伍探索 注：CI，联合指数；IC50，半数抑制浓度。
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