基于整合药理学结合GEO数据集分析开心散防治阿尔茨海默病分子机制  

Analysis on mechanism of Kaixin San in the treatment of Alzheimer disease based on integrated pharmacology and GEO chip technology

作　　者：陈晶[1] 李瑒 宋丽颖 侯志涛[1,2] Chen Jing;Li Yang;Song Liying;Hou Zhitao(Basic Medical School,Heilongjiang University of Chinese Medicine,Harbin 150040,China;Key Laboratory of Chinese Internal Medicine of Ministry of Education,Dongzhimen Hospital of Beijing University of Chinese Medicine,Beijing 100700,China)

机构地区：[1]黑龙江中医药大学基础医学院,哈尔滨150040 [2]北京中医药大学东直门医院中医内科学教育部和北京市重点实验室,北京100700

出　　处：《国际中医中药杂志》2023年第2期201-207,共7页International Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81904307);黑龙江省省属本科高校改革发展基金项目(2021CZT01);黑龙江省普通本科高等学校青年创新人才培养计划项目(UNPYSCT-2020227);黑龙江中医药大学校基金面上项目(201838);黑龙江中医药大学基础医学院青年教师科研项目(201701)。

摘　　要：目的基于整合药理学平台联合GEO芯片差异基因分析的方法,分析开心散治疗AD的作用机制。方法通过检索中医药整合药理学研究平台(TCMIP)和Drugbank数据库,获得开心散组方药物活性成分和相关分子靶点。通过GEO数据库获取GSE4757芯片数据,使用R语言获取其差异基因,绘制热图和火山图。通过Cytoscape 3.7.2构建开心散与AD的差异基因分子靶点图,使用Bisogenet和CytoNCA绘制靶点拓扑网络,并进行开心散与AD基因的GO功能富集和KEGG通路富集分析。结果获得开心散治疗AD的活性成分86个,与GEO共有的差异基因29个,构建PPI拓扑网络,筛选出核心的候选基因6个,与KEGG通路富集基因合并,获得治疗疾病的重要基因为CHRM1、CHRM2、ACHE、CHRM3、CASP8、PTGS2、DRD1、CACN1S、ADRB1。GO功能条目获得375条,主要涉及血管收缩、突触后膜可塑性,神经递质传递等。KEGG富集分析主要涉及胆碱能突触信号通路、cAMP信号通路、钙信号通路、神经-配体-受体相互作用信号通路等。结论开心散治疗AD具有多成分、多靶点、多通路的特点,可通过抑制炎症反应、降低乙酰胆碱酯酶活性、调节钙离子浓度等通路发挥治疗AD的作用。Objective To analyze the mechanism of Kaixin San in treating Alzheimer disease(AD)based on the TCM integrated pharmacology platform combined with GEO chip differential gene analysis method.Methods By searching TCMIP and Drugbank database,the active components and related molecular targets of Kaixin San were obtained.GSE4757 chip data was obtained through GEO database,and its differential genes were obtained using R language to draw heat map and volcano map.Molecular target map of differentially expressed genes between Kaixin San and AD was constructed through Cytoscape 3.7.2.Bisogenet and CytoNCA were used to draw the target topological network,and GO enrichment analysis and KEGG enrichment analysis of Kaixin San and AD gene were carried out.Results 86 active components of Kaixin San were obtained to treat AD,and 29 differential genes shared with GEO were obtained.PPI topological network was constructed.6 core candidate genes were screened,and were merged with KEGG pathway enriched genes to obtain important genes for disease treatment,such as CHRM1,CHRM2,ACHE,CHRM3,CASP8,PTGS2,DRD1,CACN1S,ADRB1.375 GO entries were obtained,mainly involving biological processes such as vasoconstriction,postsynaptic membrane plasticity,neurotransmitter transmission,etc.KEGG enrichment analysis mainly involved cholinergic synaptic signal pathway,cAMP signal pathway,calcium signal pathway,nerve ligand receptor interaction signal pathway,etc.Conclusions Kaixin San shows the features of multi-component,multi-target and multi-channel in treating AD.It can play a role in the treatment of AD by inhibiting inflammatory reaction,reducing the activity of acetylcholinesterase and regulating the concentration of calciumion.

关 键 词：阿尔茨海默病 开心散 中医药整合药理学研究平台 GEO数据库 分子对接模拟 

分 类 号：R285[医药卫生—中药学]