加味甘麦大枣汤的物质基础及其对睡眠剥夺小鼠的药效作用研究  

Study on the Material Basis and Pharmaceutical Effects of Jiawei Ganmai Dazao Decoction on Sleep-Deprived Mice

作　　者：戴梅竹 张钰成 向星亮 金姝娜 宋成武 黄荣增 DAI Mei-zhu;ZHANG Yu-cheng;XIANG Xing-liang;JIN Shu-na;SONG Cheng-wu;HUANG Rong-zeng(Jingzhou Mental Health Center,Jingzhou Hubei 434007,China;Xinrunkang Psychiatric Hospital,Wuhan 430043,China;School of Pharmacy,Hubei University of Chinese Medicine,Wuhan Hubei 430065,China)

机构地区：[1]荆州市精神卫生中心,湖北荆州434007 [2]武汉馨润康精神病医院,湖北武汉430043 [3]湖北中医药大学药学院,湖北武汉430065

出　　处：《时珍国医国药》2025年第2期266-272,共7页Lishizhen Medicine and Materia Medica Research

基　　金：湖北省自然科学基金(2023AFD151)。

摘　　要：目的考察加味甘麦大枣汤的主要化学成分,以及该方对睡眠剥夺小鼠失眠症状的改善效果。方法运用高分辨飞行时间-液质联用(UPLC-QTOF-MS/MS)技术,根据各类化合物裂解规律对化合物结构进行定性分析。通过多平台水环境法,结合自制睡眠剥夺箱建立睡眠剥夺小鼠模型,经4周给药干预,观察加味甘麦大枣汤对睡眠状况的改善作用。使用ELISA试剂盒检测大脑皮层γ-氨基丁酸(GABA)和5-羟色胺(5-HT),以及下丘脑orexin水平,探究给药对睡眠相关神经递质水平的影响。结果在加味甘麦大枣汤中共鉴定/表征出包括甘草苷、甘草酸、甘草素、芦丁、槲皮素、绿原酸、大黄素、大黄苷、五味子素和五味子醇等78个化学成分。与模型组小鼠相比,小加味甘麦大枣汤给药组光明环境和黑暗环境下的自主活动时间均显著性减少;高剂量给药组小鼠大脑皮层GABA、5-HT显著性升高;下丘脑orexin水平显著性降低。结论加味甘麦大枣汤中活性成分众多,且能显著改善睡眠剥夺小鼠的失眠状况,其机制可能涉及促进大脑皮层GABA、5-HT分泌,及抑制下丘脑orexin分泌等。Objective To examine the main chemical components of Jiawei Ganmai Dazao Decoction(JGDD)and its effectiveness in relieving insomnia in sleep-deprived mice.Methods The structure of compounds was analyzed qualitatively based on their fragmentation patterns using UPLC-QTOF-MS/MS technology.The sleep-deprived model of mice was established using the multi-platform water environment and a home-made sleep-deprived box.After a 4-week drug intervention,the improved sleep conditions were observed by adding JGDD.The levels of GABA in the cerebral cortex and 5-HT in the brain,as well as the level of orexin in the hypothalamus were detected using ELISA kits to investigate the influence of the drug on sleep-related neurotransmitter levels.Results A total of 78 chemical components were identified/characterized in JGDD,including liquiritin,glycyrrhizin,liquiritigenin,rutin,quercetin,chlorogenic acid,emodin,rheochrysin,schisandrin,and schisandrol.After 4 weeks of administration,the activity time in both light and dark environments was significantly reduced in the JGDD group.Compared with the model group,the high-dose treatment group showed a significant increase in GABA and 5-HT levels in the cerebral cortex and a significant decrease in orexin levels in the hypothalamus.Conclusion With numerous active ingredients,JGDD can significantly relieve insomnia in sleep-deprived mice.Its mechanism may involve promoting the secretion of GABA and 5-HT in the cerebral cortex,and inhibiting the secretion of orexin in the hypothalamus.

关 键 词：加味甘麦大枣汤 睡眠剥夺 液质联用 神经递质 

分 类 号：R285.5[医药卫生—中药学]