基于生物信息学探究桂枝茯苓丸治疗子宫肌瘤的作用机制

Action Mechanism of Guizhi Fuling Pills in Treatment of Uterine Fibroids Based on Bioinformatics

目的:利用生物信息学技术探究桂枝茯苓丸治疗子宫肌瘤的分子机制。方法:通过基因表达综合(GEO)数据库检索子宫肌瘤相关芯片,利用R语言分析得到差异表达基因。借助疾病数据库对子宫肌瘤已知靶基因进行检索。运用中药系统药理学数据库与分析平台(TCMSP)筛选桂枝茯苓丸的主要有效成分及作用靶基因,3组靶基因映射出关键靶点,通过基因功能注释数据库(DAVID)对关键靶基因进行基因本体(GO)及京都基因与基因组百科全书(KEGG)富集分析。结果:筛选到桂枝茯苓丸有效成分11个,对应靶点121个;GEO数据库获得差异表达基因187个,检索到子宫肌瘤相关靶标271个;3组靶标最终获得映射靶基因20个,关键靶基因9个。桂枝茯苓丸主要通过ESR1、EGFR、SRC等核心靶基因调控类固醇结合、锌离子结合等生物过程及雌激素通路、催乳素通路、GnRH通路等多个信号通路干预子宫肌瘤发生发展过程。结论:应用生物信息学具有较高的置信度和参考价值,提供了桂枝茯苓丸治疗子宫肌瘤的新方向与新思路。

Objective:To explore the molecular mechanism of Guizhi Fuling Pills in the treatment of uterine fibroids by using bioinformatics technology.Methods:The uterine fibroids related chips were searched through the NCBI GEO database,and differentially expressed genes were obtained by R language analysis.Search for known target genes of uterine fibroids with the aid of the disease database.We used the TCM System Pharmacology Database and Analysis Platform(TCMSP)to screen the main active ingredients and target genes of Guizhi Fuling Pills.The 3 sets of target genes mapped out the key targets,and gene function annotation database(DAVID)was used to gene the key target genes,Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Results:A total of 11 active ingredients of Guizhi Fuling Pills were screened,corresponding to 121 targets;187 differentially expressed genes were obtained from the GEO database,and 271 targets related to uterine fibroids were retrieved;the 3 sets of targets finally obtained 20 mapped target genes,key targets 9 genes.Guizhi Fuling Pills mainly regulated biological processes such as steroid binding and zinc ion binding through core target genes such as ESR1,EGFR,and SRC,as well as multiple signaling pathways such as estrogen pathway,prolactin pathway,and GnRH pathway to intervene in the occurrence and development of uterine fibroids.Conclusion:The application of bioinformatics has a high degree of confidence and reference value,and provides new directions and new ideas for Guizhi Fuling Pills in the treatment of uterine fibroids.