基于网络药理学的半夏-橘红药对治疗代谢综合征的作用机制探析  

Mechanism of Pinelliae Rhizoma-Citri Exocarpium Rubrum in Treatment of Metabolic Syndrome Based on Network Pharmacology

作　　者：于嘉祥 王安娜 郑一[1] 郭鹤[1] 姜楠[1] 杨宇峰[1] 石岩[1] YU Jia-xiang;WANG An-na;ZHENG Yi;GUO He;JIANG Nan;YANG Yu-feng;SHI Yan(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China)

机构地区：[1]辽宁中医药大学,沈阳110847

出　　处：《中国实验方剂学杂志》2020年第21期118-128,共11页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：辽宁省“兴辽英才计划”青年拔尖人才项目(XLYC1807145);沈阳市科学技术计划项目(18-013-0-82);辽宁省教育厅科学研究项目(L201711);国家重点基础研究发展计划(973计划)项目(2013CB532004)。

摘　　要：目的:通过网络药理学研究方法,研究二陈汤中君、臣药物半夏-橘红治疗代谢综合征的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)数据库检索半夏、橘红2味中药的有效成分,并用毒药物动力学(ADME)参数进行筛选,运用网络药理学在线数据库(TCMID),BATMAN-TCM,SymMap,TCM-MESH数据库并结合相关文献检索结果对TCMSP所获得的有效成分进行补充。利用TCMSP靶点预测模型预测药物可能的作用靶点。检索TTD,DRUGBANK,DisGeNET,CTD,GeneCards,OMIM,PharmGkb,京都基因与基因组百科全书(KEGG),DiGSeE数据库,获取代谢综合征的疾病靶点,从GEO数据库下载并分析芯片GSE98895,筛选正常人和代谢综合征患者的差异基因,对代谢综合征的疾病靶点数据库进行补充。用Rstudio 3.6.2取得半夏、橘红药物靶点与代谢综合征疾病靶点的交集。将上述交集靶点导入Metascape数据库中,进行模块分析和整体GO生物过程,KEGG和Reactome通路分析。用cytohubba插件从交集靶点筛选出核心靶点,将核心基因导入BioGPS,Genecards数据库分析核心靶点的组织分布和亚细胞分布,用DisGeNET数据库对核心靶点进行蛋白归属。结果:共筛选出半夏、橘红34个有效成分,120个作用靶点,经Rstudio3.6.2取交集后,共得出115个靶点。Metascape模块分析和整体分析的结果基本一致,主要涉及神经活动配体-受体相互作用,钙离子,环磷酸鸟苷-通过蛋白激酶G(cGMP-PKG),胆碱能突触,甲状腺激素,胰岛素等生物过程。cytohubba插件筛选出17个靶点,涉及VEGFA,NOS3等17个关键基因。核心靶点的组织分布和亚细胞分布主要为淋巴母细胞,CD33+Myeloid细胞,杏仁体,松果体和细胞质基质,线粒体等。其主要的蛋白归属为信号分子、激酶、核酸。结论:半夏-橘红药对治疗代谢综合征通过血液循环,神经活动配体-受体相互作用,cGMPPKG,白细胞介素,钙离子相关作用等复杂的生物过程�Objective:By the method of network pharmacology,the mechanism of Pinelliae Rhizomaand Citri Exocarpium Rubrum in the treatment of metabolic syndrome was explored. Method: Effective components of Pinelliae Rhizoma and Citri Exocarpium Rubrum were retrieved by TCMSP database,and then selected by ADME parameters. TCMID,BATMAN-TCM,Sym Map,TCM-MESH database were used to supplement effective components of TCMSP. TCMSP target prediction model was used to predict potential targets of drugs. DRUGBANK,Dis Ge NET,CTD,Gene Cards,OMIM,Pharm Gkb,KEGG,Di GSe E databases were retrieved to obtain the targets of metabolic syndrome,and the chips were downloaded and analyzed through GEO database No. GSE98895 to screen out the differential genes of normal people and patients with metabolic syndrome,and supplement the target databases of metabolic syndrome. The intersections of Pinelliae RhizomaCitri Exocarpium Rubrum and metabolic syndrome disease targets were obtained by Rstudio 3.6.2. The above intersection targets were imported into the Metascape database for module analysis and overall GO(Biological Process),KEGG and Reactome pathway analysis. The core targets were selected from the intersection targets by using the cytohubba plug-in,the core genes were input into the database of Bio GPS,Genecards to analyze the tissue distribution and subcellular distribution,and the core targets were assigned by using the database of Dis Ge NET. Result:A total of 34 active components and 120 targets of Pinelliae Rhizoma and Citri Exocarpium Rubrum were screened out,and 115 targets were obtained after the intersection of Rstudio 3.6.2. The results of Metascape module analysis and whole analysis were mostly the same,mainly involving the biological processes,such as ligand receptor interaction,calcium ion,c GMP-PKG,cholinergic synapse,thyroid hormone,insulin. The cytohubba plug-in was used to screen out 17 targets,involving 17 key genes,such as VEGFA and NOS3. The tissue and subcellular distribution of the core targets mainly included lymphoblasts

关 键 词：半夏 橘红 药对 二陈汤 网络药理学 代谢综合征 核心靶点 

分 类 号：R285[医药卫生—中药学] R289[医药卫生—中医学]