基于生物信息学和网络药理学探究左金丸治疗幽门螺杆菌相关性溃疡的分子机制

Exploring the molecular mechanism of Zuojin Pill in treating Helicobacter pylori related ulcers based on bioinformatics and network pharmacology

目的运用网络药理学和生物信息学方法探究左金丸治疗幽门螺杆菌(Hp)相关性溃疡(PU)所涉及的分子机制及关键基因。方法通过TCMSP数据库筛选左金丸的活性成分及作用靶点;通过GEO数据库检索Hp感染胃黏膜上皮的基因表达谱芯片数据;对芯片数据进行均一化处理并分析差异表达microRNA;利用Starbase搜索显著性差异表达microRNA靶基因;提取左金丸作用靶点和Hp相关性PU关键致病基因的交集;采用Metascape对交集基因进行GO功能分析;运用GSEA对交集基因进行KEGG通路富集分析。结果检索到44种左金丸活性成分和891个作用靶点;从GSE19769芯片中筛选出10个显著性差异表达microRNA;查找到显著性差异表达microRNA靶基因684个;取两者交集得到BIRC5、HIF1A、HSP90AB1等特异性基因;GO功能分析涉及翻译后蛋白修饰、细胞周期调节等生物过程,细胞质、细胞核等细胞成分,蛋白连接酶结合、蛋白质结合等分子功能;左金丸治疗Hp相关性PU涉及的信号通路包括MAPK信号通路、WNT信号通路、癌症相关通路等。结论结果表明左金丸治疗Hp相关性PU主要通过调控BIRC5、HIF1A、HSP90AB1等关键基因参与构成的MAPK信号通路、WNT信号通路等发挥作用。

Objective To explore the molecular mechanisms and key genes involved in the treatment of Helicobacter pylori(Hp)associated ulcers(PU)with Zuojin Pills using network pharmacology and bioinformatics methods.Methods Screening the active ingredients and targets of Zuojin Wan through the TCMSP database;The gene expression profile microarray data of Hp infected gastric mucosa epithelium were retrieved from GEO database;Homogenize the chip data and analyze differentially expressed microRNAs;Using Starbase to search for significantly differentially expressed microRNA target genes;Extract the intersection of the action target of Zuojin Pill and the key pathogenic genes of Hp related PU;Metascape was used to analyze GO functional analysis of crossing genes;Using GSEA to perform KEGG pathway enrichment analysis on intersecting genes.Results Retrieved 44 active ingredients and 891 action targets of Zuojin pill;10 significantly differentially expressed microRNAs were screened from the GSE19769 chip;684 differentially expressed microRNA target genes were found;Obtain specific genes such as BIRC5,HIF1A,and HSP90AB1 by intersecting the two;GO functional analysis involves biological processes such as post-translational protein modification and cell cycle regulation,cell components such as cytoplasm and nucleus,and molecular functions such as protein ligase binding and protein binding;The signaling pathways involved in the treatment of Hp related PU with Zuojin pill include MAPK signaling pathway,WNT signaling pathway,cancer related pathway,etc.Conclusion The results indicate that the treatment of Hp related PU with Zuojin pill mainly plays a role by regulating the MAPK signaling pathway and WNT signaling pathway composed of key genes such as BIRC5,HIF1A,and HSP90AB1.