湿毒膏治疗EGFR-TKIs所致痤疮样皮疹网络药理学研究

Network Pharmacology of Shidu Ointment in the Treatment of EGFR-TKIs Induced Acneiform Eruptions

目的探讨湿毒膏治疗表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)所致痤疮样皮疹的功效物质基础和药理学作用机制。方法通过中药系统药理学数据库和分析(TCMSP)数据库检索湿毒膏全方4味中药的化学成分,运用Genecards人类基因组注释数据库检索湿毒膏中药物所含成分及痤疮样皮疹的关联基因,导入Cytoscape 3.6.0软件分析,分别构建湿毒膏药物成分-基因靶点网络及痤疮样皮疹-基因靶点网络,使用Merge功能将上述2个网络合并,获得湿毒膏药物成分治疗痤疮样皮疹的基因靶点,使用ClueGO插件分析生物进程和KEGG通路,筛选出显著富集的生物进程和KEGG通路。结果湿毒膏药物成分作用于治疗痤疮样皮疹有21个相关基因靶点,生物进程主要富集在包括表皮生长因子受体-2信号通路、蛋白激酶B信号正向调控、磷脂酰肌醇磷酸化等;KEGG通路主要富集在表皮生长因子受体信号通路、磷脂酶D信号通路、血管表皮生长因子信号通路及多个肿瘤信号通路等。结论该研究中可初步得出湿毒膏治疗EGFR-TKIs所致痤疮样皮疹的物质基础和药理作用机制,可为进一步深入揭示其作用机制提供参考。

Objective To investigate the efficacy material basis and pharmacological mechanism of Shidu Ointment in the treatment of epidermal growth factor receptor-tyrosine kinase inhibitors( EGFR-TKIs) induced acneiform eruptions. Methods The chemical constituents of 4 traditional Chinese medicines( TCM) were retrieved by systematic TCM pharmacology database and analysis platform( TCMSP). Genecards human genome annotation database was utilized to retrieve the correlation genes of drug components in Shidu Ointment and acneiform eruptions,respectively,to construct the component-gene target network of Shidu Ointment and acneiform eruptions-gene target network by importing the data into Cytoscape 3. 6. 0 software. Merge function was used to incorporate the above two networks to obtain the Shidu Ointment composition in treating acneiform eruptions of target genes. ClueGO plug-in was utilized to analyze KEGG pathway and biological process of genes,and significant enrichment was selected to study the mechanism of Shidu Ointment.Results There were 21 related gene targets in the treatment of acneiform eruptions by screening. Biological processes were mainly concentrated in the epidermal growth factor receptor-2 signaling pathway,positive regulation of protein kinase B signal,phosphatidylinositol phosphorylation,etc. KEGG mainly enriched in epidermal growth factor receptor signaling pathway,phospholipase D signaling pathway,vascular epidermal growth factor signaling pathway,multiple tumor signaling pathways. Conclusion This study has preliminarily provided the material basis and mechanism of pharmacological effects of Shidu Ointment in the treatment of EGFR-TKIs induced acneiform eruptions,which provides reference for further research on its action mechanism.