基于网络药理学研究补阳还五汤干预缺血性脑卒中神经血管单元的作用机制

目的利用网络药理学方法研究补阳还五汤治疗缺血性脑卒中涉及的重要信号通路和保护神经血管单元的作用机制。方法使用TCMSP、上海有机所中药与化学成分数据库和相关文献获取并筛选补阳还五汤的活性成分及作用靶点;使用DrugBank数据库、药物靶标数据库(TTD)、在线人类孟德尔遗传数据库(OMIM)和GeneCards数据库获取缺血性脑卒中靶点。使用Cytoscape 3.7.2软件建立活性成分-治疗靶点网络,分析网络获取关键靶点。使用Metascape数据库对治疗靶点进行GO富集分析和KEGG信号通路富集分析。使用AlzData数据库分析治疗靶点的基因表达情况。结果通过网络分析,获得了补阳还五汤治疗缺血性脑卒中的关键靶点,包括前列腺素内过氧化物合酶2、前列腺素内过氧化物合酶1、毒蕈碱型乙酰胆碱受体M1、β2肾上腺素能受体等;通过富集分析获取了补阳还五汤治疗缺血性脑卒中的多条关键信号通路,包括PI3K-Akt信号通路、钙信号通路、IL-17信号通路、血小板活化、Apelin信号通路、NF-κB信号通路、AMPK信号通路和花生四烯酸代谢通路等;通过基因表达分析了补阳还五汤对不同组织细胞的作用,发现治疗靶点在内皮细胞、星形胶质细胞、小胶质细胞、少突胶质细胞、少突胶质细胞前体细胞和神经元中调控多种生物过程、细胞组成和分子功能。结论补阳还五汤治疗缺血性脑卒中具有多成分、多靶点、多通路、联系复杂的特点,在基因的细胞表达层面与神经血管单元密切相关,治疗作用机制包括神经保护、神经发生、抗血栓、促血管再生、胶质细胞调控等。

Study on effects on neurovascular unit of Buyang-Huanwu Decoction in the treatment of ischemic stroke based on network pharmacology

Objective To explore important signaling pathways and effects on neurovascular unit of Buyang-Huanwu Decoction in the treatment of ischemic stroke.Methods Used TCMSP database,Chinese Medicine and Chemical Composition Database of Shanghai institute of Organic Chemistry and searched related literature to obtain and screen the active compounds and their targets of Buyang-Huanwu Decoction.DrugBank database,OMIM database,TTD database and GeneCards database were used to obtain targets of ischemic stroke.Metascape database was used to carry out KEGG pathway enrichment analysis on therapeutic targets.AlzData database was used to analyze the gene expression of therapeutic targets in different cells.Results Through network analysis,the key targets of Buyang-Huanwu Decoction in the treatment of ischemic stroke were obtained,including PTGS2,PTGS1,CHRM1,ADRB2,CHRM2,F10,F7,HIF1A,PDE3A,ADRA1B and CHRM3,etc.Through enrichment analysis,multiple key signaling pathways of Buyang-Huanwu Decoction in the treatment of ischemic stroke were obtained,including PI3K-Akt signaling pathway,calcium signaling pathway,IL-17 signaling pathway,platelet activation,Apelin signaling pathway,NF-κB signaling pathway,AMPK signaling pathway and arachidonic acid metabolism,etc.Through gene expression analysis,the effect of Buyang-Huanwu Decoction on different cells was analyzed,and it was found that the targets regulate a variety of biological processes,cellular components and molecular functions in endothelial,astrocytes,microglia,oligodendrocytes,oligodendrocyte precursor cells(OPCs)and neurons.Conclusion Buyang-Huanwu Decoction is characterized by multiple components,multiple targets,multiple pathways and complex connections in the treatment of ischemic stroke,and its effect is closely related to neurovascular units(NVU)at the cellular expression level of genes,and the mechanism of therapeutic effect included neuroprotection,neurogenesis,antithrombotic,vascular regeneration,glial cell regulation,etc.