黄芪治疗幽门螺杆菌相关性消化性溃疡的靶向自噬基因生物学功能分析及其核心基因筛选  

Biological function of targeted autophagy genes of Huangqi(Astragalus membranaceus)in the treat⁃ment of Hp-associated PU and screening of the core genes

作　　者：仇婧玥 吴嫚婷 宋厚盼[1,2,3] 喻昶 熊萌 孙启芳 茹凯月 隆采玲 曾梅艳 QIU Jingyue;WU Manting;SONG Houpan;YU Chang;XIONG Meng;SUN Qifang;RU Kaiyue;LONG Cailing;ZENG Meiyan(Hunan Provincial Key Laboratory of Diagnostic Research in Chinese Medicine,Hunan University of Chinese Medicine,Changsha 410208,China;不详)

机构地区：[1]湖南中医药大学中医诊断学湖南省重点实验室,长沙410208 [2]湖南中医药大学中医学院 [3]湖南中医药大学中医心肺病证辨证与药膳食疗重点研究室

出　　处：《山东医药》2022年第21期20-25,共6页Shandong Medical Journal

基　　金：国家自然科学基金青年科学基金项目(81703920);湖湘青年科技创新人才项目(2021RC3101);湖南省教育厅科学研究重点项目(21A0240);湖南中医药大学校级科研基金项目(2020XJJJ012);湖南中医药大学研究生创新项目(2021CX46)。

摘　　要：目的分析黄芪治疗幽门螺杆菌(Hp)相关性消化性溃疡(PU)的靶向自噬基因生物学功能,并筛选黄芪治疗Hp相关性PU的靶向自噬核心基因。方法通过中药系统药理学数据库与分析平台(TCMSP)并查阅文献筛选黄芪有效活性成分,在TCMSP平台和SwissTargetPrediction平台中预测其靶基因。通过GEO数据库GSE98641数据集、StarBase、miRTarBase,筛选Hp相关性PU显著性差异表达基因。在人类自噬数据库(HADb)筛选人类自噬基因。利用Venny平台获得三者交集基因,即为黄芪治疗Hp相关性PU的靶向自噬基因。在Metascape平台对黄芪治疗Hp相关性PU的靶向自噬基因做基因本体(GO)分析与京都基因与基因组百科全书(KEGG)富集分析。在STRING平台构建黄芪治疗Hp相关性PU靶向自噬基因的蛋白质互作(PPI)网络,利用Cytohubba插件筛选黄芪治疗Hp相关性PU的靶向自噬核心基因。结果筛选得到黄芪有效活性成分的靶基因2941个、Hp相关性PU显著性差异表达基因2109个、人类自噬基因232个,取交集后共获得黄芪治疗Hp相关性PU靶向自噬基因16个。黄芪治疗Hp相关性PU靶向自噬基因的GO功能主要涉及细胞凋亡信号通路、有丝分裂细胞周期G1/S的转变、丝氨酸/苏氨酸蛋白激酶复合物、蛋白质结构域特异性结合、蛋白激酶活性等,KEGG信号通路主要包括癌症通路、细胞凋亡通路、NOD样受体信号通路等。筛选获得TP53、CDKN1A、CCND1、CDK1、CDK2、CDK4、CCND2、E2F1、RB1、CCND3等10个黄芪治疗Hp相关性PU靶向自噬核心基因。结论黄芪治疗Hp相关性PU的靶向自噬基因可能通过细胞凋亡、细胞周期等生物学过程发挥作用,与癌症通路、细胞凋亡通路、NOD样受体信号通路等信号通路有关;TP53、CDKN1A、CCND1、CDK1、CDK2、CDK4、CCND2、E2F1、RB1、CCND3等10个基因可能是黄芪治疗Hp相关性PU的靶向自噬核心基因。Objective To analyze the biological function of the targeted autophagy genes of Huangqi(Astragalus membranaceus)in the treatment of Helicobacter pylori(Hp)-associated peptic ulcer(PU),and to screen the core genes in it.Methods The active ingredients of Huangqi were collected in Traditional Chinese Medicine Database and Analysis Platform(TCMSP),and their possible target genes were predicted in TCMSP and Swisstargetprediction.Through GEO database GSE98641 dataset,StarBase,miRTarBase,we screened the significantly differentially expressed genes of Hp-related PU.Human autophagy related genes were screened from the human autophagy database(HADb).We used the Venny platform to obtain the three intersection genes,which were the targeted autophagy genes of Huangqi in the treatment of Hp-associated PU.Gene Ontology(GO)analysis and enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG)were carried out on Metascape platform,and the protein-protein interaction(PPI)network of targeted autophagy genes were constructed on STRING platform.Cytohubba was used to screen the core targeted autophagy genes.Results Totally 2941 target genes of effective active ingredients of Huangqi,2109 genes with significant differential expression of Hp-associated PU,and 232 human autophagy genes were screened out.After the intersection,a total of 16 target autophagy genes were obtained.GO function of these targeted autophagy genes mainly involved apoptosis signal pathway,G1/S transition of mitotic cell cycle,serine/threonine protein kinase complex,protein domain specific binding,protein kinase activity,etc.And their KEGG signal pathway mainly included cancer pathway,apoptosis pathway,NOD-like receptor signal pathway,etc.Ten targeted core autophagy genes were screened out,including TP53,CDKN1A,CCND1,CDK1,CDK2,CDK4,CCND2,E2F1,RB1,and CCND3.Conclusions The targeted autophagy genes of Huangqi in the treatment of Hp-associated PU may play a role through biological processes such as apoptosis and cell cycle,and are related to cancer pathway,a

关 键 词：黄芪 幽门螺杆菌 消化性溃疡 自噬 网络药理学 生物信息学 

分 类 号：R573.1[医药卫生—消化系统]