基于GEO数据库联合网络药理学研究川芎-赤芍药对治疗动脉粥样硬化的药理过程及分子机制  

Pharmacological Process and Molecular Mechanism of Chuanxiong Rhizoma-Radix Paeoniae Rubra Drug Pair in the Treatment of Atherosclerosis Based on GEO Database Combined with Network Pharmacology

作　　者：陈启庭[1] 林洪[1] 陈利捷 卓超林 岳双冰[1] 金宇[1] 张淼 CHEN Qiting;LIN Hong;CHEN Lijie;ZHUO Chaolin;YUE Shuangbing;JIN Yu;ZHANG Miao(Dept.of Integrated Chinese and Western Medicine,Shenzhen Second People’s Hospital,Guangdong Shenzhen 518000,China;Graduate School,Guangxi University of Traditional Chinese Medicine,Nanning 530001,China)

机构地区：[1]深圳市第二人民医院中西医结合科,广东深圳518000 [2]广西中医药大学研究生院,南宁530001

出　　处：《中国医院用药评价与分析》2024年第6期655-661,共7页Evaluation and Analysis of Drug-use in Hospitals of China

基　　金：国家自然科学基金青年基金项目(No.82104770);广东省基础与应用基础研究基金项目(No.2022A1515011456)。

摘　　要：目的:探讨活血化瘀中药药对川芎-赤芍拮抗动脉粥样硬化的潜在分子机制及药理过程。方法:使用R语言Limma包分析GEO数据库GSE43292数据集,对有表达差异的动脉粥样硬化基因进行筛选和提取。川芎-赤芍药对所含的化学活性组分及靶点通过中药系统药理学数据库与分析平台检索。合并差异基因和药物作用靶点以获得共同的靶点。利用在线分析工具STRING和Cytoscape构建药物和靶点的调控网络以及靶点间的蛋白质-蛋白质相互作用(PPI)网络。然后利用R语言注释靶点基因的基因本体(GO)功能,分析京都基因与基因组百科全书(KEGG)通路,再进行基因集富集分析(GSEA)以验证KEGG的通路和富集的情况,确定靶点基因的调控功能和参与基因调控功能的信号转导通道。结果:共筛选出动脉粥样硬化差异基因1244个,川芎-赤芍药对含36个生物活性成分,其中靶点为环加氧酶1、肾上腺素受体、过氧化物酶体增殖物激活受体-γ、激酶插入域受体、孕激素受体、基质金属蛋白酶9、CXC趋化因子配体8、蛋白激酶Cβ、白细胞介素6、CD14、二肽基肽酶-4、PIK3CG、肾上腺素受体α1B、微管相关蛋白2、尿激酶纤溶酶原激活剂和单胺氧化酶B。靶点在GO中主要富集在合成DNA过程的调控、DNA生物合成的过程、含胶原的细胞外基质、细胞外基质、蛋白酶结合、细胞迁移、血管形成过程、膜筏结构、转录的调节等与动脉粥样硬化炎症、脂肪代谢及血管生成相关的生物学注释。脂质与动脉粥样硬化通路和核因子κB信号通路与动脉粥样硬化关系最为密切,并且在KEGG信号通路和GSEA均显示出富集。结论:川芎-赤芍药对通过潜在的13个活性成分作用于可能的16个靶点调控相关信号转导通路,通过抗炎、调脂和保护血管等方式产生抗动脉粥样硬化的作用。OBJECTIVE:To probe into the potential molecular mechanism and pharmacological process and molecular mechanism of blood-activating and stasis-removing traditional Chinese medicine(TCM)drug pair of Chuanxiong rhizoma-Radix paeoniae rubra in the treatment of atherosclerosis.METHODS:R language limma package was used to analyze GSE43292 dataset of GEO database,the genes of atherosclerosis with differential expression were screened and extracted.The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was retrieved for the chemical active components and targets in Chuanxiong rhizoma-Radix paeoniae rubra drug pair.Differential genes and drug targets were combined to obtain common targets.Online analysis tools of STRING and Cytoscape were used to construct regulatory network of drugs and targets and protein-protein interaction(PPI)network between targets.R language was used to annotate gene ontology(GO)function of the target genes,analyse the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway,and perform Gene Set Enrichment Analysis(GSEA)to validate the KEGG pathway and enrichment.The regulatory functions of target genes and signal transduction channels involved in gene regulatory functions were determined.RESULTS:A total of 1244 differential genes of atherosclerosis were screened out,and the Chuanxiong rhizoma-Radix paeoniae rubra drug pair contained 36 bioactive components,the targets were respectively PTGS1,AR,PPARG,KDR,PGR,matrix metalloproteinase 9,CXC chemokine ligand 8,PRKCB,interleukin 6,CD14,DPP4,PIK3CG,ADRA1B,MAP2,PLAU and MAOB.The targets in GO were mainly enriched in the regulation of synthetic DNA process,process of DNA biosynthesis,collagen-containing extracellular matrix,extracellular matrix,protease binding,cell migration,angiogenesis process,membrane raft structures,regulation of transcription and other biological annotations related to atherosclerotic inflammation,lipid metabolism and angiogenesis.Lipid and atherosclerosis pathway and nuclear factorκB signaling pathway wer

关 键 词：川芎-赤芍药对 动脉粥样硬化 GEO数据库联合网络药理学 信号通路 

分 类 号：R932[医药卫生—生药学] R96[医药卫生—药学]