基于入血成分-靶点-通路策略探索丹参-川芎-葛根角药配伍对脑心同治的科学内涵  

Scientific Connotation of Ternary Compatibility of Danshen-Chuanxiong-Gegen(丹参-川芎-葛根)in Naoxintongzhi(脑心同治)Based on the Strategy of Component in Plasma-Target-Pathway

作　　者：汤依娜[1] 李晓媛 郭慧 袁崇均[1] 陈帅[1] 罗森[1] 郭俊霞[1] 李青苗[1] 谭正怀[1] Tang Yina;Li Xiaoyuan;Guo Hui;Yuan Chongjun;Chen Shuai;Luo Sen;Guo Junxia;Li Qingmiao;Tan Zhenghuai(Sichuan Provincial Key Laboratory of Quality and Innovation Research of Chinese Materia Medica,Sichuan Academy of Chinese Medicine Sciences,Chengdu 610041;School of Pharmaceutical Sciences,Zhengzhou University,Zhengzhou 450001)

机构地区：[1]四川省中医药科学院中药材品质及创新中药研究四川省重点实验室,成都610041 [2]郑州大学药学院,郑州450001

出　　处：《中药药理与临床》2022年第6期31-41,共11页Pharmacology and Clinics of Chinese Materia Medica

基　　金：四川省科技计划项目(编号:2019YJ0617);四川省中医药管理局科学技术研究专项课题(编号:2021ZD006);中医药产业发展重大项目(编号:510201202109711)。

摘　　要：目的:基于入血-成分-靶点-通路的策略,初步探析角药配伍丹参-川芎-葛根(简称“通脉方”)治疗缺血性心、脑血管疾病相关中医药理论“理、法、方、药”及“脑心同治”之内涵,为临床合理应用提供科学依据。方法:大鼠灌胃丹参-川芎-葛根水提物,采用UPLC-MS法,检测鉴别代谢入血成分,根据实测提取物、入血成分及通脉方成分分析相关文献,筛选通脉方活性成分的范围,通过本草组鉴(HERB)、Swiss Target Prediction、GeneCards等数据库检索活性成分所对应的靶点以及缺血性心、脑血管疾病相关靶点;获取成分与疾病的交集靶点,采用STRING平台和Cytoscape可视化软件构建丹参-川芎-葛根活性成分-靶点网络及蛋白互作(PPI)网络;经拓扑学条件过滤,筛选核心靶点网络;运行R语言脚本对PPI网络进行差异基因富集分析,获得富集排名前列的基因和信号通路;采用AutoDock Vina软件将高连接度的活性成分与核心靶点进行分子对接。结果:在丹参-川芎-葛根水提物中检测到14种成分,大鼠给药后血浆中检测到11个入血原型成分,有大豆苷元、染料木素、3′-甲氧基大豆苷元、芒柄花素、隐丹参酮、等,同时也是核心靶点所映射的成分。分子对接结果显示这些成分与靶蛋白受体具有较强的结合能力(结合能<-7.0 kcal/mol)。通脉方“脑心同治”机理涉及的“脑”、“心”共同点包括:缺血性心、脑血管疾病各自的成分-靶点调控网络中,有多个共同的靶基因和靶基因映射相连的通脉方成分;由22个核心靶点构成的核心蛋白互作网络(PPI)中,其中21个为共同靶点,与核心靶点相映射的通脉方成分相同(23个);差异基因富集分析中,有9项共同的生物过程(BP),8项共同的分子功能(MF),15条显著影响的共同信号通路,其中基因占比最高的通路均为PI3K/AKT信号通路;心、脑疾病核心靶点调控网络映射的入血成分(11个)相同�Objective:To explore the scientific connotation of ternary compatibility of Salviae Miltiorrhizae Radix et Rhizoma(Danshen)-Chuanxiong Rhizoma(Chuanxiong)-Puerariae Lobatae Radix(Gegen)"(abbreviated as Tongmai Formula(通脉方))for the treatment of ischemic cardiovascular and cerebrovascular diseases in Li(理),Fa(法),Fang(方),Yao(药),and Naoxintongzhi(脑心同治)in traditional Chinese medicine(TCM)based on the strategy of the component in plasma-target-pathway and provide a scientific basis for the rational clinical application.Methods:Rats were administered with the water extract of Tongmai Formula by gavage,and the metabolites in plasma were detected by UPLC-MS.Then,the active components of Tongmai Formula were screened according to the measured extracts,components in plasma,and related literature on the analysis of components of Tongmai Formula.Targets corresponding to bioactive components of Tongmai Formula and relevant targets of ischemic heart disease(IHD)and ischemic cerebrovascular disease(ICD)were retrieved from the databases such as HERB,Swiss Target Prediction,and GeneCards.The intersection targets of drug components and diseases(IHD and ICD)were obtained.STRING platform and Cytoscape software were employed to construct the active component-target network and protein-protein interaction(PPI)network.The core target network was screened out by filtering with topological conditions.Differential gene enrichment analysis was conducted for the PPI network by running the R language script,and the top genes and signaling pathways were obtained.AutoDock Vina software was used to conduct molecular docking of the active components with high connectivity and the core targets.Results:Fourteen components were detected in the water extract of Tongmai Formula,while 11 prototypes were found in rat plasma after drug administration,including daidzein,genistein,formononetin,3’-methoxydaidzein,and cryptotanshinone,which were also the components mapped by the core targets.The molecular docking results showed that t

关 键 词：丹参 川芎 葛根 角药 入血化学成分 脑心同治 

分 类 号：R285[医药卫生—中药学]