目的 基于网络药理学研究川芎挥发油抗心绞痛的作用机制，并用动物实验加以验证。方法 通过水蒸气蒸馏法、气相色谱-质谱联用仪(gas chromatography-mass spectrometry，GC-MS)、口服利用度(oral bioavailability，OB)筛出挥发油成分;使用Pubchem、SwissTarget、DisGeNET、DrugBank数据库和R语言分别获取挥发油成分的靶点、心绞痛的靶点和交集靶点;蛋白质-蛋白质相互作用通过String数据库完成;使用R语言的ClusterProfiler包对交集靶点进行基因本体分析(gene ontology，GO)和京都基因与基因组百科全书分析(Kyoto Encyclopedia of Genes and Genomes，KEGG)富集分析，并通过Cytoscape构建中药-成分-靶点-通路网络;借助AutoDock vina 1。2。3、Pymol 3。0、Discovery Studio 2016软件进行分子对接，分析关键靶点和主要挥发油成分的亲和力。最后，通过动物实验进一步验证川芎挥发油对心绞痛的治疗效果。结果 网络药理学研究共得到10个挥发油成分和22个关键靶点，这些靶点与神经递质、突触膜上的受体、物质代谢等生物过程以及神经活性配体-受体相互作用、视黄醇代谢、药物代谢-细胞色素P450等通路密切相关;分子对接结果表明3-butylidenephthalide、Alpha-selinene、Trans-ligustilide等挥发油成分与多个关键靶点结合发挥治疗作用。动物实验表明川芎挥发油通过调节射血分数(ejection fraction，EF)、短轴缩短率(fractional shortening，FS)、左室收缩末内 径(left ventricular internal diameter in systole，LVIDs)和每搏输出量(stroke volume，SV)水平以及乳酸脱氢酶(lactate dehydrogenase，LDH)、肌酸激酶(creatine kinase，CK)、天冬氨酸转氨酶(aspartate aminotransferase，AST)活性，促进受损心肌细胞中ADRA1A、CHRM5蛋白的表达，改善心肌纤维状态，减小细胞间隙，减少炎性细胞浸润表现出保护心肌的作用。结论 川芎挥发油具有有效保护受损心肌组织，治疗心绞痛的作用。
Network pharmacological study and experimental validation of Rhizoma Chuanxiong volatile oil in the treatment of angina pectoris
Objective Network pharmacology and animal experiments were performed to study and verify the therapeutic effect of Rhizoma Chuanxiong volatile oil on angina pectoris.Methods Volatile oil components were screened using steam distillation,gas chromatography-mass spectrometry,and oral bioavailability.Targets of these components were identified using Pubchem,SwissTarget,DisGeNET,and DrugBank databases as well as R language.Angina pectoris-related targets and intersection targets were obtained.Protein-protein interactions were analyzed using the STRING database.The ClusterProfiler package in R was used to analyze the gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment of the intersecting targets,and Cytoscape was used to construct herbal-component-target-pathway networks.Molecular docking analysis was conducted using AutoDock Vina 1.2.3,Pymol 3.0,and Discovery Studio 2016 software to evaluate the affinity between key targets and the main volatile oil components.Finally,the therapeutic effect of Rhizoma Chuanxiong volatile oil on angina pectoris was verified by animal experiments.Results In total,10 volatile oil components and 22 key targets were identified.They were closely related to neurotransmitters,receptors on synaptic membranes,material metabolism,neuroactive ligand-receptor interaction,retinol metabolism,and drug metabolism-cytochrome P450 pathways.The molecular docking result showed that 3-butylidenephthalide,alpha-selinene,trans-ligustilide,and other volatile oil components combined with several key targets play therapeutic roles.Animal experiments showed that the volatile oil of Rhizoma Chuanxiong can regulate the ejection fraction,fractional shortening,stroke volume,and left ventricular internal diameter in systole and the activities of lactate dehydrogenase,creatine kinase and aspartate aminotransferase;promote the expression of ADRA1A and CHRM5 proteins in damaged cardiomyocytes;improve the state of myocardial fibers;reduce intercellular space;and reduce inflammatory cell infiltration.Conclusions The volatile oil of Ligusticum wallichii can effectively protect damaged myocardial tissue and thus has a role in treating angina pectoris.
万方数据
维普
