芪银三两三验方治疗靶向药相关性皮疹的分子机制研究

Study on the Molecular Mechanism of Qiyin Sanliangsan in the Treatment of Targeted Drug-related Rash

目的探寻芪银三两三验方核心用药组成的分子作用机制,通过网络药理学分析,构建“芪银三两三-药物有效成分-关键性作用靶点-靶向药相关性皮疹对应靶点”的可视化网络关系。方法基于中药系统药理学数据库和分析平台(TCMSP)、中药作用机制在线分析系统(BATMAN-TCM),对芪银三两三验方核心用药的作用成分和有效靶点进行筛选,通过核心复方靶点垂钓,提取复方中的生物学活性成分及有效靶点。通过药物不良反应靶点分类系统(ADReCS-Target)得到靶向药相关性皮疹对应靶点。通过STRING数据库构建蛋白质相互作用可视化网络图(PPI),并应用Cytoscape3.8.2软件进行网络拓扑分析,筛选关键性作用靶点。采用DAVID v6.8数据库对关键性靶点进行通路富集,预测芪银三两三验方中核心用药组成可能的分子生物学机制。结果经检索得到核心处方中有效生物学活性成分118种,潜在预测靶点328个,靶向药相关性皮疹对应靶点214个,将二者相互匹配得到核心处方有效成分-靶向药相关性皮疹共同作用靶点86个,其中包括8个关键性靶点;复方对210个生物学过程及81条信号通路能产生重要影响。结论芪银三两三验方治疗靶向药相关性皮疹的潜在作用机制,可能是通过PI3K-Akt信号通路及细胞因子-细胞因子受体相互作用等信号转导,调节角质层细胞增殖与分化,修复EGFR-TKI引起的皮肤损伤,这为今后的药物研发及相关临床研究提供了参考方向。

Objective:To explore the molecular mechanism of the core drug composition of Qiyin Sanliangsan,and to construct the visual network relationship of“Qiyin Sanliangsan-active ingredients of drugs-key action targets-corresponding targets of targeted drug-related rash”through network pharmacology analysis.Methods:Based on TCMSP and BATMAN-TCM,the active ingredients and effective targets of Qiyin Sanliangsan core drugs were screened,and the bioactive ingredients and effective targets in the compound were extracted by fishing for the core compound target.The corresponding targets of targeted drug-related rash were obtained by ADReCS-Target.Protein-protein interaction(PPI)was constructed by STRING database,and Cytoscape 3.8.2 software was used to analyze the network topology and screen the key targets.DAVID v6.8 database was used to enrich the key targets and predict the possible molecular biological mechanism of the core drug composition in Qiyin Sanliangsan.Results:Totally 118 kinds of effective bioactive ingredients in the core prescription were retrieved,including 328 potential predicted targets,214 corresponding targets of targeted drug-related rash,and 86 common targets of active ingredients in the core prescription targeted drug-related rash were obtained by matching the two,including 8 key targets;the compound had important effects on 210 biological processes and 81 signaling pathways.Conclusion:The potential mechanism of Qiyin Sanliangsan in the treatment of targeted drug-related rash may be through signal transduction such as PI3K-Akt signaling pathway and cytokine-cytokine receptor interaction,regulating the proliferation and differentiation of stratum corneum cells,and repairing skin lesions caused by EGFRTKI,which provides a reference direction for future drug research and development and related clinical research.