基于网络药理学探讨脑络欣通治疗急性脑梗死的作用机制  

Investigating the action mechanism of TCM compound Naoluo Xintong in treating acute cerebral infarction based on network pharmacology

作　　者：李鼎文 王艳昕[2] 稳晓 胡泰然 张明 LI Dingwen

机构地区：[1]安徽中医药大学研究生院,安徽合肥230038 [2]安徽中医药大学第一附属医院,安徽合肥230031

出　　处：《中医临床研究》2021年第32期12-17,共6页Clinical Journal Of Chinese Medicine

摘　　要：目的:本研究采用网络药理学的方法探讨脑络欣通中药复方治疗急性脑梗死的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)收集并筛选脑络欣通中药成分及其相关作用靶点,利用OMIM、Gene Cards数据库分别收集急性脑梗死的相关疾病靶点;应用Venny 2.1在线作图平台获取疾病和中药相互作用交集靶点,导入STRING 11.0数据库作相互作用分析,得到核心蛋白基因,并构建蛋白质-蛋白质相互作用网络图,筛选并获得药物治疗疾病的核心靶点,再通过Cytoscape3.7.2软件构建"中药-成分-核心靶点-疾病"网络图;将上述获得核心基因导入DAVID平台,进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。结果:得到脑络欣通中药复方中药有效成分66个,作用靶点208个,其中山柰酚、槲皮素、β-谷甾醇、木犀草素等为其主要活性成分。经筛选得到疾病基因1870个。共获得中药-疾病交集基因133个,核心靶点22个,其中包括丝氨酸/苏氨酸蛋白激酶1(AKT Serine/Threonine Kinase 1,AKT1)、白细胞介素-6(Interleukin 6,IL-6)、内皮型一氧化氮合酶(Endothelial Nitric Oxide Synthase,e NOS或NOS3)、血管内皮生长因子A(Vascular Endothelial Growth Factor A,VEGFA)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、白细胞介素-1β(Interleukin 1 Beta,IL1B)等。GO富集分析共涉及生物过程(Biological Process,BP)1530个,细胞组分(Cellular Component,CC)12个,分子功能(Molecular Function,MF)40个。KEGG通路富集分析显示蛋白主要富集在丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)信号通路、肿瘤坏死因子(Tumor Necrosis Factor,TNF)信号通路、晚期糖基化终末产物-糖基化终末产物受体(AGE-RAGE)信号通路、C型凝集素受体信号通路等。结论:本研究表明脑络欣通治疗急性脑梗死具有"多成分-多靶点-多途径"的特点与优势,为进一步研究脑络欣通治疗急性脑梗死的Objective:In this study,network pharmacology was used to investigate the action mechanism of TCM compound Naoluo Xintong(脑络欣通)in treating acute cerebral infarction.The components of Naoluo Xintong and its related targets were collected and screened in TCMSP database.The related disease targets of acute cerebral infarction were selected in OMIM and GeneCards databases respectively.The intersection targets of the interaction between diseases and Chinese medicine compound were obtained by Venny 2.1 online drawing platform,and were imported into the STRING 11.0 database for an interaction analysis.The core protein genes were obtained,and PPI network diagram was structured.The core targets of medicines on diseases were screened and obtained.Then,the network diagram of“TCM-components-core targets-diseases”was constructed by Cytoscape 3.7.2 software.The above core genes were imported into the DAVID platform to perform the GO analysis and KEGG pathway enrichment analysis.Results:59 active components and 208 target sites were obtained from Chinese medicine compound Naoluo Xintong,among which kaempferol,quercetin,β-sitosterol and luteolin were the main active components.A total of 1870 disease genes were screened from the disease database,133 Chinese materia medica-disease intersection genes were obtained,and 22 core targets were screened,including AKT1,IL-6,NOS3,VEGFA,TNF,IL1 B,etc..The GO enrichment analysis involved 1530 BP,12 CC and 40 MF.The KEGG pathway enrichment analysis showed that proteins were mainly enriched in MAPK signaling pathway,TNF signaling pathway,AGE-RAGE signaling pathway,C-type lectin receptor signaling pathway and so on.Conclusion:This study shows that Naoluo Xintong has the characteristics and advantages of“multi-component,multi-target,and multi-pathway”in treating acute cerebral infarction.It provides a theoretical basis for further study on the material basis and molecular mechanism of Naoluo Xintong on acute cerebral infarction.

关 键 词：网络药理学 脑络欣通 急性脑梗死 作用机制 

分 类 号：R285[医药卫生—中药学]