越鞠丸挥发油通过调节神经递质和缓解神经炎症治疗高原睡眠障碍  

Yueju volatile oil treats high altitude sleep disturbance by modulating neurotransmitters and alleviating neuroinflammation

作　　者：李爱 杨建豪 李佳巧 高月 胡鹏翼 胡慧璇 杨明 郑琴[1,2] LI Ai;YANG Jian-hao;LI Jia-qiao;GAO Yue;HU Peng-yi;HU Hui-xuan;YANG Ming;ZHENG Qin(Key Laboratory of Modern Preparation of TCM,Ministry of Education,Jiangxi University of Chinese Medicine,Nanchang 330004,China;Jiangxi Provincial Key Laboratory of Improvement and Innovation of Traditional Chinese Medicine,Nanchang 330004,China;Academy of Military Medicine,Academy of Military Sciences,Chinese People's Liberation Army,Beijing 100850,China;National Key Laboratory of Modern Chinese Medicine Creation of Classic Prescriptions of Jiangxi University of Traditional Chinese Medicine,Nanchang 330103,China)

机构地区：[1]江西中医药大学,现代中药制剂教育部重点实验室,江西南昌330004 [2]中药改良创新江西省重点实验室,江西南昌330004 [3]中国人民解放军军事科学院军事医学研究院,北京100850 [4]江西中医药大学,经典名方现代中药创制全国重点实验室,江西南昌330103

出　　处：《药学学报》2025年第4期976-988,共13页Acta Pharmaceutica Sinica

基　　金：中药研制与中药安全性创新团队(ZYYCXTD-D-202207);中药制剂技术与装备创新团队(CXTD22006)。

摘　　要：本文主要探讨越鞠丸挥发油(Yueju volatile oil,YJVO)治疗高原睡眠障碍(high altitude sleep disturbance,HASD)小鼠的药效和作用机制。采用气相色谱-质谱联用技术(gas chromatography-mass spectrometry,GC-MS)对YJVO成分进行鉴定,应用网络药理学预测YJVO治疗HASD的作用机制。将KM小鼠随机分为对照组(control)、模型组(model)、YJVO-L、M、H组(200、400、800μL·m^(-3)),地西泮组(diazepam,DZP,2 mg·kg^(-1)),除对照组外其余置于低压氧舱中诱导HASD模型。动物实验经江西中医药大学伦理委员会批准(伦理号:TEMPOR20230088)。以协同睡眠实验和负重游泳实验测试YJVO睡眠调节效果;H&E染色法观察下丘脑、海马脑组织的损伤情况;采用酶联免疫法(ELISA)检测脑组织中褪黑素(melatonin,MT)、γ氨基丁酸(γ-aminobutyric acid,GABA)、白介素-6(interleukin-6,IL-6)、白介素-1β(interleukin-1beta,IL-1β)和血浆中五羟色胺(5-hydroxytryptamine,5-HT)、食欲素-A(orexin-A)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)含量,并测定丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-PX)生化指标;Western blot检测NF-κB/NLRP3通路中关键蛋白的表达;免疫组化法检测海马、下丘脑组织中五羟色胺1A受体(5-hydroxytryptamine 1A receptor,5-HT_(1A))的表达。GC-MS结果显示,YJVO共鉴定出68个成分。网络药理学结果显示YJVO治疗HASD机制涉及AGE-RAGE、TNF、血清素、NF-κB等多条信号通路。行为学实验结果表明,YJVO可显著增加小鼠的睡眠时长,缩短睡眠潜伏期,并提高其体能和抗疲劳能力(P<0.01)。H&E结果显示,HASD小鼠海马、下丘脑组织病理损伤得到明显改善。ELISA结果显示YJVO上调脑组织中促眠递质MT、GABA,下调血浆促觉醒递质orexin-A、5-HT水平,并减少IL-6、IL-1β、TNF-α炎症因子分泌(P<0.01)。生化结果表明,YJVO能抑制HASD小鼠脑组织中MDA生成,并提�To investigate the effect and underlying mechanism of action of Yueju volatile oil(YJVO)in the treatment of high altitude sleep disturbance(HASD)mice,gas chromatography-mass spectrometry(GC-MS)was used to identify the components of YJVO,while network pharmacology was applied to predict the mechanism of action.KM mice were selected and randomly assigned to several groups:the control group(control),the model group(model),and the YJVO treatment groups at low(YJVO-L,200μL·m^(-3)),medium(YJVO-M,400μL·m^(-3)),and high(YJVO-H,800μL·m^(-3))doses,as well as the diazepam group(DZP,2 mg·kg^(-1)).Except for the control group,all mice were subjected to a hypobaric oxygen chamber to establish the HASD model.Animal experiments were approved by the Animal Ethics Committee of Jiangxi University of Traditional Chinese Medicine(ethics No.:TEMPOR20230088).Co-sleeping and weight-bearing swimming experiments were conducted to assess the sleepregulating effects of YJVO.Hematoxylin and eosin(H&E)staining was employed to observe damage in hypothalamic and hippocampal brain tissues.Enzyme-linked immunosorbent assay(ELISA)was utilized to measure levels of melatonin(MT),γ-aminobutyric acid(GABA),interleukin-6(IL-6),interleukin-1beta(IL-1β),5-hydroxytryptamine(5-HT),orexin-A,and tumor necrosis factor-α(TNF-α)in both plasma and brain tissues.Concurrently,malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione peroxidase(GSH-PX)were detected to evaluate oxidative stress.Western blot was used to determine the expression of key proteins in the NF-κB/NLRP3 pathway,and immunohistochemistry(IHC)was used to detect the expression of 5-hydroxytryptamine1A receptor(5-HT_(1A))in hippocampal and hypothalamic tissues.The GC-MS results revealed that YJVO was identified to contain 68 components.Network pharmacology results indicated that the mechanism of YJVO in treating HASD involves multiple signaling pathways such as AGE-RAGE,TNF,serotonin,and NF-κB.Behavioral experiments indicated that YJVO significantly prolonged the sleep duration,

关 键 词：越鞠丸挥发油 低压低氧 高原睡眠障碍 神经炎症 神经递质系统 网络药理学 GC-MS分析 

分 类 号：R966[医药卫生—药理学]