细胞膜固相色谱法联合网络药理学探讨补阳还五汤促进缺血性脑卒中康复的作用

Effect of Buyang Huanwutang on Rehabilitation of Ischemic Stroke by Cell Membrane Solid-phase Chromatography Combined with Network Pharmacology

目的:采用细胞膜固相色谱法联合网络药理学探讨补阳还五汤促进缺血性脑卒中康复的作用机制。方法:细胞膜固相色谱法筛选补阳还五汤供试液中与海马神经元细胞特异性结合的成分;检索PubChem,PharmMapper,在线人类孟德尔遗传数据库(OMIM),GeneCards等数据库获取特异性结合成分的作用靶点及缺血性脑卒中疾病的靶点;借助STRING,Cytoscape 3.7.1软件绘制蛋白质-蛋白质相互作用(PPI)网络;利用DAVID在线数据库对PPI网络中的核心靶点进行基因本体(GO)功能富集分析及京都基因与基因组百科全书(KEGG)生物途径分析,探讨补阳还五汤促进缺血性脑中风康复可能的作用机制。结果:通过细胞膜固相色谱法,筛选出了13个与海马神经元细胞特异性结合的成分;通过网络分析和靶点富集,显示作用靶点主要关联细胞增殖调控、蛋白质磷酸化、缺氧反应、血管生成等生物过程,对叉头转录因子(FoxO)信号通路、腺苷酸激活蛋白激酶(AMPK)信号通路、核转录因子-κB(NF-κB)信号通路、细胞凋亡通路等具有广泛的干预作用。结论:补阳还五汤可能通过调节FoxO,AMPK,NF-κB,细胞凋亡等信号通路促进缺血性脑中风的康复。

Objective:To explore the effect of Buyang Huanwutang(BHD)on rehabilitation of ischemic stroke(IS)by cell membrane solid-phase chromatography and network pharmacology.Method:Cell membrane solid-phase chromatography was performed to screen the specific binding components of BHD with hippocampal neurons.Targets of the specific components were retrieved based on PubChem and PharmMapper and those of IS were searched from Online Mendelian Inheritance in Man(OMIM)and GeneCards.Then,the protein-protein interaction(PPI)network was constructed with STRING and Cytoscape 3.7.1,followed by Gene Ontology(GO)term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment of the hub genes in the PPI network.Thereby,the mechanism of BHD in promoting IS rehabilitation was clarified.Result:A total of 13 specific components were identified.The hub genes were mainly involved in the biological processes of regulation of cell proliferation,protein phosphorylation,hypoxia response,and angiogenesis,and the pathways of Forkhead box O(FoxO)signaling pathway,adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)signaling pathway,nuclear factor kappa B(NF-κB)signaling pathway,and apoptosis pathway.Conclusion:BHD may promote the recovery of IS by regulating FoxO,AMPK,NF-κB,and apoptosis pathways.