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OACSTPCD

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 factor κB signaling pathway were most closely related to atherosclerosis,which showed enrichment in both KEGG signaling pathway and GSEA.CONCLUSIONS:Chuanxiong rhizoma-Radix paeoniae rubra drug pair regulates the relevant signal transduction pathways through potential 13 active components by acting on 16 possible targets,and achieves anti-atherosclerotic effects through anti-inflammatory,lipid-regulating and blood vessel protection.