目的 基于网络药理学和动物实验探究落花生Arachis hypogaea枝叶（PSL）治疗失眠症的作用机制。方法 借助数据库和在线平台筛选PSL活性成分及其靶点，以及失眠症相关靶点，利用Venny 2.1.工具获取PSL与失眠症交集靶点，并通过STRING数据库对交集靶点进行蛋白质-蛋白质相互作用（protein-protein interaction，PPI）分析。利用Cytoscape 3.9.1软件进行拓扑分析筛选出核心靶点，并对核心靶点进行基因本体（gene ontology，GO）功能注释及京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路富集分析。通过构建对氯苯丙氨酸（parachlorophenylalanine，PCPA）诱导的失眠大鼠模型对网络药理学结果进行体内实验验证。结果 网络药理学结果表明PSL治疗失眠症可能与丝氨酸/苏氨酸蛋白激酶1（serine/threonine-protein kinase 1，AKT1）、多巴胺D1受体（dopamine receptor D1，DRD1）、多巴胺D2受体（dopamine receptor D2，DRD2）、γ-氨基丁酸A型受体1（γ-aminobutyric acid receptor A1，GABRA1）等靶点以及血清素能突触、环磷酸腺苷（cyclic adenosine monophosphate，cAMP）信号通路、谷氨酸能突触、多巴胺能突触及胆碱能突触等通路相关。动物实验结果显示，PSL显著减少失眠大鼠的运动距离、运动速度和运动时间（P＜0.01），增加静止时间（P＜0.01），使其运动轨迹有序，从而改善大鼠的失眠以及焦虑样行为；PSL能够改善大鼠海马神经元病理形态，显著上调下丘脑中5-羟色胺（serotonin，5-HT）、γ-氨基丁酸（γ-aminobutyric acid，GABA）、GABA/谷氨酸（glutamic acid，Glu）水平以及γ-氨基丁酸A型受体α1（γ-aminobutyric acid receptor Aα1，GABAAα1）、AKT1的表达（P＜0.05、0.01、0.001），并显著下调下丘脑中Glu、多巴胺（dopamine，DA）水平及DRD1表达和血清中肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-1β（interleukin-1β，IL-1β）水平（P＜0.05、0.01）。结论PSL可能通过调节5-HT、Glu、GABA和DA等神经递质以及AKT1、TNF-α、IL-1β等炎症物质，从而治疗失眠症。

Objective To explore the mechanism of Arachis hypogaea stems and leaves (PSL) in treating insomnia based on network pharmacology and animal experiments. Methods The active ingredients and targets of PSL, as well as insomnia related targets, were screened using databases and online platforms. The intersection targets of PSL and insomnia were obtained using Venny 2.1 tool, and protein-protein interaction (PPI) analysis was performed on the intersection targets using STRING database. Cytoscape 3.9.1 software was used to perform topology analysis for screening core targets, gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis on core targets were performed. The network pharmacology results were validated in vivo by constructing a rat model of insomnia induced by parachlorophenylalanine (PCPA). Results The results of network pharmacology showed that the treatment of insomnia with PSL may be related to targets such as serine/threonine protein kinase 1 (AKT1), dopamine receptor D1 (DRD1), dopamine receptor D2 (DRD2), γ-aminobutyric acid receptor A1 (GABRA1), as well as pathways such as serotonergic synapses, cyclic adenosine monophosphate (cAMP) signaling pathway, glutamatergic synapses, dopaminergic synapses and cholinergic synapses. Animal experiment results showed that PSL significantly reduced the movement distance, speed and time of insomnia rats (P < 0.01), increased the resting time (P < 0.01), and made their movement trajectory orderly, thereby improving insomnia and anxiety like behavior in rats; PSL could improve the pathological morphology of hippocampal neurons in rats, significantly up-regulate the levels of serotonin (5-HT), γ-aminobutyric acid (GABA), GABA/glutamate (Glu) as well as the expressions of γ-aminobutyric acid receptor Aα1 (GABAAα1) and AKT1 in hypothalamus (P < 0.05, 0.01, 0.001), and significantly down-regulate the levels of Glu, dopamine (DA) and DRD1 expression in hypothalamus as well as the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in serum (P < 0.05, 0.01). Conclusion PSL may treat insomnia by regulating neurotransmitters such as 5-HT, Glu, GABA and DA, as well as inflammatory substances such as AKT1, TNF-α and IL-1β.

R285.5

国家重点研发计划项目(2021YFC2501500);上海市治未病优势技术规范项目[ZY (2021-2023)-0104-02-GF-04]