基于网络药理学联合GEO数据库及分子对接探究脑安胶囊治疗缺血性脑卒中的作用  

Role of Naoan capsules in treatment of ischemic stroke by network pharmacology combined with GEO database and molecular docking

作　　者：杨淑贤 孙阿宁 朱斌[1] 史卫忠[1] 赵志刚[1] YANG Shu-xian;SUN A-ning;ZHU Bin;SHI Wei-zhong;ZHAO Zhi-gang(Department of Pharmacy,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China)

机构地区：[1]首都医科大学附属北京天坛医院药学部,北京100070

出　　处：《中国临床药理学杂志》2024年第3期435-439,共5页The Chinese Journal of Clinical Pharmacology

基　　金：北京市医院管理局临床医学发展专项扬帆计划基金资助项目(ZYLX201827)。

摘　　要：目的 基于网络药理学、基因表达综合数据库及分子对接技术,预测及初步验证脑安胶囊(NAC)治疗缺血性脑卒中(IS)的作用机制。方法 用中药系统药理学分析平台收集NAC中的活性成分,用基因表达综合数据库筛选疾病相关差异基因。筛选获得两者的共同靶标后,用Cytoscape 3.8.2软件构建化合物-疾病网络;同时创建蛋白质-蛋白质相互作用网络以确定NAC治疗IS的候选靶点,并且进行基因本体和京都基因与基因组百科全书富集分析。最后用分子对接技术对核心靶点进行初步验证。结果 共筛选出56个候选化合物和18 544个疾病相关差异基因,进一步通过化合物-疾病网络发现,槲皮素、山柰酚、木犀草素和黄芩素可能是NAC治疗IS的关键活性化合物。在PPI网络核心查找中,筛选到了NAC治疗IS的8个关键靶点,包括丝裂原活化蛋白激酶1(MAPK1)、B-细胞淋巴瘤因子2(Bcl-2)和半胱氨酸天冬氨酸蛋白酶3(CASP3)等。NAS治疗IS的关键通路主要富集在脂质和动脉粥样硬化、糖基化终末产物与其受体系统(AGE-RAGE)、肿瘤坏死因子(TNF)、白细胞介素17(IL-17)、C-型凝集素受体、凋亡、缺氧诱导因子-1(HIF-1)、MAPK等信号通路。最后,分子对接结果表明关键活性化合物(槲皮素、山柰酚、木犀草素和黄芩素)与8个关键靶点均有较好的结合力,初步验证了网络药理学的结果。结论 NAC可通过多成分、多靶点、多通路发挥治疗IS的作用。Objective To predict and verify the mechanism of Naoan capsules (NAC) in treatment of ischemic stroke (IS) by network pharmacology,Gene Expression Omnibus (GEO) database,and molecular docking technology.Methods The active components in NAC were collected using the Traditional Chinese Medicine System Pharmacological Analysis Platform,and the disease-related differential genes were screened using GEO database.After screening and obtaining the common targets of the two,the compound disease network was constructed by Cytoscape 3.8.2 software.At the same time,proteinprotein interaction networks were created to identify candidate targets for NAC treatment of IS,and gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses were performed.Finally,core targets were verified by molecular docking technology.Results A total of 56candidate compounds and 18 544 disease-related differential genes were screened.Further,quercetin,kaempferol,luteolin and baicalein were found to be the key active compounds of NAC in the treatment of IS through the compound disease network.In the search of PPI network core,eight key targets for NAC treatment of IS were screened,including mitogen-activated protein kinase 1 (MAPK1),B-cell lymphoma factor 2(Bcl-2),cysteinylaspartate specific protease 3 (CASP3),etc.In addition,the key pathways of NAC treatment of IS are mainly concentrated in lipid and atherosclerosis,advanced glycation end products and receptor for advanced glycation end products (AGE-RAGE),tumor necrosis factor (TNF),interleukin17 (IL-17),C-type lectin receptor,apoptosis,hypoxia-inducing factor-1 (HIF-1),MAPK and other signaling pathways.Finally,the molecular docking results showed that the key active compounds (quercetin,kaempferol,luteolin and baicalein) had good binding force with the 8 key targets,which initially verified the results of network pharmacology.Conclusion NAC plays a role in the treatment of IS through multi-component,multi-target and multi-pathway.

关 键 词：脑安胶囊 缺血性脑卒中 基因表达综合数据库 网络药理学 分子机制 

分 类 号：R972[医药卫生—药品]