基于网络药理学探讨加味通窍活血汤治疗瘀血阻窍型后循环缺血的作用机制  

Mechanism of Jiawei Tongqiao Huoxue Decoction in Treating Posterior Circulation Ischemia of Blood Stasis Induced Orifice Obstructing Based on Network Pharmacology

作　　者：张道培 刘梦琳 张怀亮[1] ZHANG Daopei;LIU Menglin;ZHANG Huailiang(The First Affiliated Hospital of Henan University of Chinese Medicine/Center for Diagnosis and Treatment of Vertigo in Henan Province/Institute of Vertigo in Henan University of Chinese Medicine,Zhengzhou Henan China 450000)

机构地区：[1]河南中医药大学第一附属医院/河南省眩晕病诊疗中心/河南省中医药大学眩晕病研究所,河南郑州450000

出　　处：《中医学报》2023年第10期2138-2147,共10页Acta Chinese Medicine

基　　金：河南省省级科技研发计划联合基金项目(优势学科培育类)(222301420080);2022年度河南省高等学校重点科研项目(22A320036);河南省中医药科学研究专项课题重点项目(2019ZY1013)。

摘　　要：目的:基于网络药理学探讨加味通窍活血汤治疗瘀血阻窍型后循环缺血的作用机制。方法:通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)检索加味通窍活血汤组方中药麝香、川芎、赤芍、桃仁、红花、全蝎、石菖蒲、葛根、老葱、生姜、大枣的活性成分和作用靶点。利用Genecards数据库及在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)检索后循环缺血相关靶点,并与中药有效成分相关靶点取交集。将交集靶标导入String11.0中获取蛋白质互作网络(protein-protein interaction networks,PPI)并筛选核心靶点。运用Cyoscape 3.7.2软件构建“中药-成分-靶点”网络并进行拓扑分析。借助R软件进行基因本体(gene ontology,GO)功能富集分析及京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)信号通路富集分析。通过Autodock Vina对筛选出的部分活性成分与核心靶点进行分子对接。结果:通过TCMSP数据库检索加味通窍活血汤组方中药活性成分,并获得加味通窍活血汤相关靶点289个。在Genecards和OMIM数据库获得疾病靶标1044个,与中药活性成分靶点交集靶标131个。PPI网络分析筛选出10个核心基因。“中药-成分-靶点”网络分析显示槲皮素、17-β-雌二醇、木犀草苷、山柰酚、β-谷甾醇、黄芩素、β-胡萝卜素、芒柄花黄素、豆甾烯醇、杨梅酮为核心活性成分。GO功能富集分析显示主要与对缺氧的反应及氧化应激的反应等生物过程、细胞因子受体结合等分子功能及膜微区等细胞组分相关。KEGG通路富集分析筛选得到156条信号通路。分子对接显示,核心成分与关键靶点能有效结合。结论:加味通窍活血汤中的槲皮素、17-β-雌二醇、木犀草苷等有效成分可能通过作用于血管内皮生长因子A(vascular endothelial growth factor,VEGObjective:To explore the mechanism of Jiawei Tongqiao Huoxue Decoction in treating posterior circulation ischemia due to blood stasis and obstruction of orifices based on network pharmacology.Methods:The active components and targets of musk,Ligusticum chuanxiong,Paeonia lactiflora,peach kernel,safflower,scorpion,Acorus gramineus,Pueraria lobata,onion,ginger and jujube in Jiawei Tongqiao Huoxue Decoction were searched by means of traditional Chinese medicine database and analysis platform(TCMSP).The related targets of posterior circulation ischemia were searched by Genecards database and online human mendelian inheritance database(OMIM),and the targets were intersected with the related targets of effective components of traditional Chinese medicine.Protein interaction networks(PPI)were obtained by introducing the intersection targets into String11.0,and the core targets were screened.Using Cyoscape 3.7.2 software,the network of"Traditional Chinese Medicine-Component-Target"was constructed and its topology was analyzed.The function enrichment analysis of geneontology(GO)and the signal pathway enrichment analysis of Kyoto encyclopedia of genes and genomes(KEGG)were carried out with the help of R software.The molecular docking of some screened active components with core targets was carried out by AutodockVina.Results:The active components of Jiawei Tongqiao Huoxue Decoction were searched by TCMSP database,and 289 related targets of Jiawei Tongqiao Huoxue Decoction were obtained.1044 disease targets were obtained from Genecards and OMIM databases,and 131 targets intersected with the targets of active ingredients of traditional Chinese medicine.PPI network analysis screened out 10 core genes.The network analysis of"traditional Chinese medicine-component-target"shows that quercetin,17-β-estradiol,luteolin,kaempferol,β-sitosterol,baicalein,β-carotene,formononel and myricetin are the core active components.GO function enrichment analysis shows that it is mainly related to biological processes such as response to hypo

关 键 词：加味通窍活血汤 瘀血阻窍证 后循环缺血 血管重塑 作用机制 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]