基于网络药理学的侯氏黑散抗缺血性脑卒中机制研究  

A network pharmacology approach to uncover the molecular mechanisms of Houshiheisan for treatment of ischemic stroke

作　　者：王璇 马重阳 张雅文 程宏发 张秋霞 Wang Xuan;Ma Chongyang;Zhang Yawen;Cheng Hongfa;Zhang Qiuxia(Beijing Key Lab of Traditional Chinese Medicine Collateral Disease Theory Research,Department of Clinical Basic Science of Traditional Chinese Medicine,School of Traditional Chinese Medicine,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学中医药学院中医临床基础学学系中医络病研究北京市重点实验室,北京100069

出　　处：《首都医科大学学报》2021年第1期43-52,共10页Journal of Capital Medical University

基　　金：国家自然科学基金项目(81373526,81873224)。

摘　　要：目的应用网络药理学方法分析侯氏黑散抗脑缺血的核心组分及分子机制。方法通过侯氏黑散活性成分筛选、成分靶点和疾病靶点挖掘,建立并分析“成分-靶点”网络得到药效成分及药效靶点。构建蛋白相互作用(protein-protein interaction,PPI)网络进行京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析,找出潜在信号通路。结果筛选得到了侯氏黑散抗脑缺血的5个有效成分:β-谷甾醇、隐品碱、原阿片碱、豆甾醇、山姜素;22个药效靶点:雌激素受体1(estrogen receptor,ESR1)、雄激素受体(androgen receptor,AR)、前列腺素G/H合酶2(prostaglandin G/H synthase 2,PTGS2)、凝血酶原2(prothrombin,F2)、内皮型一氧化氮合酶(nitric oxide synthase,endothelial,NOS3)等。基于PPI网络,侯氏黑散抗脑缺血的靶点显著富集于流体剪切应力通路、晚期糖基化终产物-晚期糖基化终产物受体(advanced glycation end products/receptor for advanced glycation end products,AGE-RAGE)通路、缺氧诱导因子1-α/血管内皮生长因子(hypoxia inducible factor1-α/vascular endothelial growth factor,HIF1-α/VEGF)通路等。结论侯氏黑散抗脑缺血损伤主要通过影响炎性反应、血管新生、氧化应激等方面发挥作用,与多条信号通路存在直接或间接关系,具有多成分、多靶点、多途径的特点。Objective To analyze the core components and possible molecular mechanisms of Houshiheisan in the treatment of cerebral ischemia by network pharmacological method.Methods Through active components screening,components targets and disease targets prediction of Houshiheisan,the“component-target”network was established and analyzed to obtain the effective components and targets.Protein-protein interaction(PPI)network was constructed for Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis to identify potential signal pathways.Results Five effective components of Houshiheisan against cerebral ischemia,includingβ-Sitosterol,cryptopine,fumarine,stigmasterol,and(2R)-7-hydroxy-5-methoxy-2-phenylchroman-4-one,and 22 important anti-cerebral ischemia targets,including estrogen receptor(ESR1),androgen receptor(AR),prostaglandin G/H synthase 2(PTGS2),prothrombin(F2),nitric oxide synthase,endothelial(NOS3),etc.were found.Based on the PPI results,pharmacological targets of Houshiheisan treating cerebral ischemia might have a close relationship with the fluid shear stress pathway,advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)pathway,and hypoxia inducible factor1-α/vascular endothelial growth factor(HIF1-α/VEGF)pathway,etc.Conclusion Houshiheisan for treatment of ischemic stroke mainly plays a role in regulating inflammation,angiogenesis,and oxidative stress.It holds direct or indirect relationships with multiple signal pathways and has the characteristics of multi-components,multi-targets,and multi-pathways.

关 键 词：网络药理学 侯氏黑散 缺血性脑卒中 分子机制 

分 类 号：R229[医药卫生—中医基础理论]