基于益肾填精理论与网络药理学探讨熟地黄-山茱萸药对治疗注意缺陷多动障碍的潜在治疗作用与机制  

Exploration of the potential therapeutic effect and mechanism of Shudihuang-Shanzhuyu on attention deficit hyperactivity disorder based on the thought of kidney-tonifying and essence-filling and network pharmacology

作　　者：熊馨 刘芳[2] Xiong Xin;Liu Fang(Liaoning University of Traditional Chinese Medicine,Shenyang Liaoning 110847;Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang Liaoning 110032)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]辽宁中医药大学附属医院,辽宁沈阳110032

出　　处：《山西中医药大学学报》2023年第3期273-282,共10页Journal of Shanxi University of Chinese Medicine

摘　　要：目的:采用网络药理学方法研究熟地黄-山茱萸药对治疗注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)的潜在治疗作用及其可能的作用机制。方法:通过TCMSP、PubChem、SwissTargetPrediction数据库及查阅文献获取熟地黄-山茱萸药对的主要作用成分与作用靶点。利用Cytoscape 3.9.1软件将药对成分、靶点绘制为可视化网络图。检索OMIM、TTD、DrugBank、GeneCards数据库得到ADHD相关靶点,利用Uniprot数据库将药对和ADHD靶点转化为对应基因名。疾病与药物靶点取交集获得熟地黄-山茱萸药对治疗ADHD的潜在靶点,将结果导入STRING数据库,得到蛋白互作PPI网络图,并对PPI网络进行拓扑分析,得到药对治疗疾病的核心靶点。利用Metascape网络平台分别进行基因本体GO功能和KEGG通路富集分析,将分析结果绘制为气泡图,最终得到药对治疗ADHD的“主要活性成分-关键靶点-通路”网络图。结果:共获得熟地黄-山茱萸药对治疗疾病的26个有效成分、199个作用靶点和1861个疾病靶点,药物与疾病的共同靶点46个。PPI网络最终筛选确定了9个关键核心靶点,分别为钠依赖性血清素转运蛋白(SLC6A4)、钠依赖性多巴胺转运蛋白(SLC6A3)、肿瘤坏死因子-α(TNF-α)、乙酰胆碱酯酶(ACHE)、糖皮质激素受体(NR3C1)、β-淀粉状蛋白A4(APP)、胺氧化酶(含黄素)A(MAOA)、神经元乙酰胆碱受体蛋白α-7链(CHRNA7)、雌激素受体α(ESR1)。GO生物过程分析发现靶点主要集中于神经递质转运、神经元-神经胶质细胞信号传导和肾上腺素能受体信号通路参与调解的肾上腺素-去甲肾上腺素的调节、多巴胺的过程和儿茶酚胺的转运过程等。KEGG通路富集分析得到45条作用通路,主要为神经活性配体-受体相互作用、钙信号通路、心肌细胞中的肾上腺素能信号传导等。结论:熟地黄-山茱萸药对可能通过多靶点、多成分、多途径对ADHD发挥潜在治疗Objective:To explore the potential therapeutic effect and possible mechanism of Shudihuang-Shanzhuyu on attention deficit hyperactivity disorder(ADHD)based on network pharmacology.Methods:The main active components and target of drug pair of Shudihuang-Shanzhuyu were obtained through TCMSP,PubChem,SwissTargetPrediction database and literature review.Cytoscape 3.9.1 software was used to map drug pair components and targets into visual network diagram.OMIM,TTD,DrugBank and GeneCards databases were searched to obtain ADHD-related targets,and Uniprot database was used to convert drug pair and ADHD targets into corresponding gene names.The intersection of disease and drug targets was used to obtain the potential targets of Shudihuang-Shanzhuyu for treating ADHD.The results were imported into STRING database to obtain the PPI network diagram of protein interaction,and the PPI network was topologically analyzed to obtain the core targets of drug pair for treating the disease.The enrichment analysis of GO function and KEGG pathway was carried out by using Metascape network platform.The analysis results were drawn as bubble diagram,and the network diagram of“main active ingredient-key target-pathway”of the drug pair in the treatment of ADHD was finally obtained.Results:A total of 26 active components,199 action targets and 1861 disease targets were obtained from the drug pair of Shudihuang-Shanzhuyu in treating ADHD.There were 46 common targets between drugs and diseases.PPI network finally screened and identified 9 key core targets,namely sodium-dependent serotonin transporter(SLC6A4),sodium-dependent dopamine transporter(SLC6A3),tumor necrosis factor-α(TNF-α),acetylcholinesterase(ACHE),glucocorticoid receptor(NR3C1),beta-amyloid protein A4(APP),amine oxidase[containing flavin]A(MAOA),neuronal acetylcholine receptor proteinα-7 chain(CHRNA7),and estrogen receptorα(ESR1).GO biological process analysis found that the targets mainly focused on the regulation of adrenaline-norepinephrine mediated by neurotransmitter t

关 键 词：注意缺陷多动障碍 熟地黄 山茱萸 益肾填精 网络药理学 作用机制 

分 类 号：R285.6[医药卫生—中药学]