摘要
目的:探究半夏白术天麻汤联合阿司匹林对短暂性脑缺血发作(TIA)模型大鼠的神经功能及缺血灶是否具有更好的改善作用,并基于网络药理学、分子对接探究半夏白术天麻汤联合阿司匹林治疗TIA的物质基础和作用机制。方法:用线栓法制备TIA模型大鼠,随机分为模型组、假手术组、西药组(阿司匹林组)、中药组(半夏白术天麻汤组)、治疗组(半夏白术天麻汤联合阿司匹林组),灌胃给药治疗7 d,对各组动物给药前后进行神经功能评分,计算各组脑梗死体积。借助中药系统药理学分析平台,PubChem、PharmMapper数据库,检索并筛选半夏白术天麻汤相关中药的化学成分及靶点,使用GeneCards数据库,以“aspirin”为关键词检索阿司匹林化学成分,检索DisGeNET在线数据库获取TIA相关靶点,利用Venny 2.1软件求得到药物-疾病之间的共同靶点,通过STRING 10.5数据库得到蛋白互作网络分析,使用Cytoscape 3.7.1软件构建药物-成分-靶点-疾病网络,使用DAVID 6.8在线数据库进行基因本体(GO)、京都基因与基因组百科全书(KEGG)通路富集分析,最后分子对接验证核心成分和核心靶点的结合能力。结果:动物实验表明,治疗组可明显提高TIA模型大鼠的神经功能评分,明显减小缺血灶面积。异黄酮、阿司匹林、儿茶素、柚皮甙、β-谷固醇和白术素Ⅲ等成分,可能是半夏白术天麻汤联合阿司匹林共同作用于TIA的关键活性物质。白细胞介素6(IL6)、肿瘤坏死因子(TNF)、白细胞介素1β(IL1B)、清蛋白(ALB)、血管内皮生长因子A(VEGFA)等可能为主要的干预靶点。同时,血脂与动脉粥样硬化、血流剪应力对动脉粥样硬化信号通路、血小板活化信号通路、肿瘤坏死因子信号通路、丝裂原活化蛋白激酶(MAPK)信号通路及白细胞介素-17(IL-17)信号通路等均为关键影响路径。分子对接研究表明,上述主要成分与靶点之间展现出良好的相互结合能力。结论:半夏白术天麻汤与阿司匹林治疗TIA具有系统性、多靶点、多通路的特点,并初步阐释了潜在的分子机制。
Objective:To explore effect of Banxia Baizhu Tianma Decoction and aspirin has a better effect on the neurological function and ischemic lesions of rats with transient ischemic attack(TIA)models,and to investigate the material basis and mechanism of action of the treatment of TIA with Banxia Baizhu Tianma Decoction combined with aspirin based on network pharmacology and molecular docking.Methods:TIA model rats were prepared using longa method,and were randomly divided into the model group,the sham operation group,the western medicine group(aspirin group),the traditional Chinese medicine group(Banxia Baizhu Tianma Decoction group),and the treatment group(Banxia Baizhu Tianma Decoction combined with aspirin group).The rats were treated by intragastric administration for 7 days.The neurological function scoring was tested before and after drug administration for each group of animals.The chemical components and targets of the traditional Chinese medicine,Banxia Baizhu Tianma Decoction were retrieved and screened through the traditional Chinese medicine system pharmacology analysis platform,PubChem and PharmMapper databases.The chemical components of aspirin were searched using the keyword"aspirin"from GeneCards database.The relevant target genes related to TIA retvieved from the DisGeNET online database.The common targets between drugs and diseases were obtained using Venny 2.1 software.Protein interaction network analysis was conducted through the STRING 10.5 database.The drug-component-target-disease network was constructed using Cytoscape 3.7.1 software.Gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed using the DAVID 6.8 online database.Finally,the binding ability of the core components and the core targets was verified through molecular docking.Results:Animal experiments showed that the treatment group could significantly improve the neurological function scores of TIA model rats and significantly reduce the area of ischemic lesions.Quercetin,aspirin,kaempferol,naringin,β-sitosterol and atractylarideⅢmight be the key active substances in the combination of Banxia Baizhu Tianma Decoction and aspirin for the treatment of TIA.Interleukin 6(IL6),tumor necrosis factor(TNF),interleukin 1β(IL1B),albumin(ALB),vascular endothelial growth factor A(VEGFA),etc.,might be the main intervention targets.Blood lipids,arterial atherosclerosis,the promotion of atherosclerosis by blood flow shear stress,platelet activation channels,tumor necrosis factor signaling pathway,mitogen-activated protein kinase(MAPK)signaling pathway,and interleukin-17(IL-17)signal transduction were all key influencing pathways.Molecular docking studies have showed that the aforementioned main components exhibited excellent binding capabilities with the target.Conclusion:Banxia Baizhu Tianma Decoction and aspirin for the treatment of TIA show the characteristics of systemic multi-target and multi-pathway effects,and the potential molecular mechanisms are preliminarily explained.
作者
李宏阳
邱金玲
杨若
凌洁
张岳阳
顾卫
LI Hongyang;QIU Jinling;YANG Ruo;LING Jie;ZHANG Yueyang;GU Wei(Huizhou Hospital of Guangzhou University of Chinese Medicine,Huizhou 516000,Guangzhou,China)
出处
《中西医结合心脑血管病杂志》
2025年第19期2926-2936,共11页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
广东省基础与应用研究基金联合基金(粤惠)项目(No.2022A1515140069)
惠州市医疗卫生领域科技计划项目(No.2022CZ010161)。
关键词
短暂性脑缺血发作
半夏白术天麻汤
阿司匹林
网络药理学
分子对接
transient ischemic attacks
Banxia Baizhu Tianma Decoction
aspirin
network pharmacology
molecular docking
