基于GEO芯片和分子对接探讨小檗碱治疗溃疡性结肠炎活动期的机制  

Investigating the Mechanism of Berberine for Treating Active Ulcerative Colitis Based on GEO Chip Data and Molecular Docking

作　　者：王喜霞 刘金响 马小兵[1] 史英[1] 张桥[2] 高二鹏 张益珊 Wang Xixia;Liu Jinxiang;Ma Xiaobing;Shi Ying;Zhang Qiao;Gao Erpeng;Zhang Yishan(The Second Affiliated Hospital,Shaanxi University of Chinese Medicine,Shaanxi,Xianyang 712000,China)

机构地区：[1]陕西中医药大学第二附属医院,陕西咸阳712000 [2]陕西中医药大学,陕西咸阳712000

出　　处：《中国中医急症》2024年第9期1508-1511,1534,共5页Journal of Emergency in Traditional Chinese Medicine

基　　金：国家自然科学基金项目(82104396);陕西省自然科学基础研究计划项目(2024JC-YBQN-0963,2022JM-506);陕西中医药大学校级科研课题项目(2021GP44);陕西中医药大学校级科研课题项目(2021YB04)。

摘　　要：目的通过GEO芯片数据和分子对接探寻小檗碱治疗溃疡性结肠炎(UC)活动期的潜在机制。方法利用PharmMapper获取小檗碱分子靶点;检索GEO数据库中UC相关芯片数据,借助R语言分析差异基因;对小檗碱分子靶标与UC差异基因进行富集分析;将小檗碱分子靶点与UC差异基因的交集作为关键基因,通过Cytoscape软件寻找潜在基因蛋白;利用分子对接技术分析小檗碱分子与UC关键基因、潜在基因蛋白的结合情况。结果筛选出小檗碱分子靶点255个;对GEO数据库的GSE107499芯片分析,筛选出860个差异基因,包括545个上调基因和315个下调基因;比对UC差异基因与小檗碱靶点KEGG富集分析,推测小檗碱治疗UC与调节趋化因子信号通路、T细胞受体信号通路及PPAR信号通路关系密切;对小檗碱治疗UC的关键基因网络拓扑分析,筛选出11个小檗碱治疗UC潜在基因蛋白,分子对接验证表明配体与受体具有较好的结合活性。结论小檗碱通过多靶点、多途径发挥对UC的治疗作用,其机制可能与调节T细胞免疫和炎症因子水平有关。Objective:To investigate the potential mechanism of berberine in the treatment of ulcerative colitis(UC)through GEO chip data and molecular docking.Methods:The molecular targets of berberine were obtained by Pharm Mapper server;the UC related chip data in GEO database were retrieved,and the differential genes were analyzed by R language;the differential genes between berberine molecular target and UC were enriched and analyzed;the intersection of berberine molecular target and UC differential genes was taken as the key gene,and the potential gene proteins were found by Cytoscape software;the binding of berberine to key genes and potential gene proteins of UC was analyzed by molecular docking technology.Results:A total of 255 molecular targets of berberine were screened;based on the analysis of GSE107499 chip in GEO database,860 differential genes were screened,including 545 up-regulated genes and 315 down-regulated genes;the functional annotation of berberine target go was mainly concentrated in the biological processes such as the regulation of transcription factors,DNA transcription and the regulation of tyrosine kinase activity;comparing the enrichment analysis of UC differential gene and berberine target KEGG,it was speculated that berberine treatment of UC was closely related to chemokine signaling pathway,T cell receptor signaling pathway and PPAR signaling pathway;through the topological analysis of the key gene network of berberine in the treatment of UC,11 potential gene proteins of berberine in the treatment of UC were selected.The molecular docking verification showed that the ligand and receptor had good binding activity.Conclusion:Berberine exerts its therapeutic effect on UC through multiple targets and pathways,and its mechanism may be related to regulation of immunity and inflammation.

关 键 词：溃疡性结肠炎 小檗碱 GEO数据挖掘 分子对接 作用机制 

分 类 号：R574.62[医药卫生—消化系统]