吴静静 邓家琳 于庆洋 闫雨柔 王俊宏

摘要 目的：基于网络药理学探讨枸杞子-五味子药对治疗注意缺陷多动障碍的药效物质基础和作用机制。方法：检索ETCM数据库，筛选枸杞子-五味子活性成分及靶基因;检索Drugbank、Genecards、DisGeNET和TTD数据库，筛选ADHD相关靶基因;利用Cytoscape构建药对活性成分-靶点网络并进行拓扑结构分析;对疾病靶點与药对靶点绘制维恩图筛选关键靶点，利用David进行GO分析和KEGG分析。结果：筛选出枸杞子-五味子有36个活性成分，207个靶基因，活性成分-靶点拓扑结构分析得到Inosine和其他基因互相关联程度最高;筛选出ADHD相关靶基因1 861个，维恩图提取关键靶点73个，GO分析得到11条生物过程，12条细胞组分表达过程，14个分子功能相关过程;KEGG分析显示21条信号通路，包括类固醇激素的合成、细胞色素P450代谢、GABA能突触及胆碱能突触调节、色氨酸代谢等。结论：枸杞子-五味子药对活性成分通过多成分、多靶点、多通路调控机体类固醇激素代谢、神经递质代谢、中枢神经系统调节、免疫调节对ADHD发挥治疗作用。

关键词 注意缺陷多动障碍;枸杞子;五味子;网络药理学;分子机制

Mechanism Study on the Investigation of the Mechanism of Fructus Lycii-Fructus Schisandrae Chinensis in the Treatment of Attention-deficit/Hyperactivity Disorder Based on Network Pharmacology

WU Jingjing，DENG Jialin，YU Qingyang，YAN Yurou，WANG Junhong

（Dongzhimen Hospital，Beijing University of Chinese Medicine，Beijing 100700，China）

Abstract Objective：To explore the molecular mechanism of Fructus Lycii-Fructus Schisandrae Chinensis in the treatment of attention-deficit/hyperactivity disorder based on network pharmacology.Methods：ETCM was used to screen the active components and target gene of Fructus Lycii-Fructus Schisandrae Chinensis.Drugbank，Genecards，DisGeNET and TTD databases was searched to screen ADHD-related target genes; Cytoscape was used to construct a drug-to-active ingredient-target network and conduct topological structure analysis; Venn diagrams for disease targets and drug-to-targets were drawn to screen key targets.David was used for GO analysis and KEGG analysis.Results：A total of 36 active ingredients and 207 potential target genes related to Fructus Lycii-Fructus Schisandrae Chinensis were retrieved from ETCM.1 861 ADHD-related target genes were screened，73 key targets were extracted from Venn diagrams.A total of 11 biological processes，12 cell component expression processes，and 14 molecular functions related processes were obtained by GO analysis; KEGG analysis showed 21 signal pathways，including the synthesis of steroid hormones，cytochrome P450 metabolism，GABAergic synapse and cholinergic synaptic regulation，tryptophan metabolism，etc.Conclusion：The active ingredients of Fructus Lycii-Fructus Schisandrae Chinensis active ingredients can regulate the body′s steroid hormone metabolism，neurotransmitter metabolism，central nervous system regulation，and immune regulation through multiple components，multiple targets，and multiple pathways to play a therapeutic effect on ADHD.

Keywords Attention deficit hyperactivity disorder; Fructus Lycii; Fructus Schisandra Chinensis; Network pharmacology; Molecular mechanism

中图分类号：R285文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.03.008

注意缺陷多动障碍（Attention Deficit Hyperactivity Disorder，ADHD）是儿童期最为常见的神经发育障碍之一，临床主要表现为与年龄不相称的注意力不集中、多动和冲动行为[1]，常与对立违抗障碍、品行障碍、抽动障碍、孤独症谱系障碍、学习困难等共存，对患儿身心健康、学业水平、家庭关系等造成负面影响。ADHD全球患病率3.4%[2]，近年来我国ADHD总患病率逐年上升，已达6.2%[3]，约2/3患者症状持续至青春期，1/3可能持续终生[4]，可见ADHD对于患儿的负面影响是长远的，给个人、家庭及整个社会带来沉重负担。……