酸枣仁炮制前后镇静催眠作用比较研究  

Comparative study on sedative and hypnotic effects of Semen Ziziphi Spinosae before and after processing

作　　者：蔡铭 陈林霖 徐波[1] 谢光璟 夏婧 CAI Ming;CHEN Lin-lin;XU Bo;XIE Guang-jing;XIA Jing(Engineering Research Center of TCM Protection Technology and New Product Development for the Elderly Brain Health,Ministry of Education,Hubei University of Chinese Medicine,Hubei University of Chinese Medicine,Wuhan 430065,China;Key Laboratory of Traditional Chinese Medicine Resource and Compound Prescription,Ministry of Education,Hubei University of Chinese Medicine,Wuhan 430065,China)

机构地区：[1]湖北中医药老年脑健康中医药防护技术与新产品研发教育部工程研究中心,湖北武汉430065 [2]湖北中医药大学教育部中药资源与复方重点实验室,湖北武汉430065

出　　处：《中国药理学通报》2024年第5期984-991,共8页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金青年项目(No 82205232);湖北省科技厅自然科学基金青年项目(No 2021CFB256)。

摘　　要：目的基于网络药理学和动物实验探讨中药酸枣仁(Semen Ziziphi Spinosae,SZS)炮制前后镇静催眠作用差异。方法通过相关平台和数据库收集SZS的化学成分,检索失眠和睡眠障碍的靶点进行检索,构建蛋白质相互作用关系,绘制出中药-成分-靶点-通路网络,并进行富集分析。结合预测结果,通过戊巴比妥诱导睡眠试验、行为学分析、脑组织相关基因mRNA水平和血浆神经递质评价SZS不同制品对昆明小鼠的影响。结果SZS与失眠相关的靶点基因共有22个,包括乙酰胆碱酯酶(acetylcholinesterase,ACHE)、α-1B肾上腺素能受体(alpha-1B adrenergic receptor,ADRA1B)、钠依赖性5-羟色胺转运蛋白[solute carrier family 6(neurotransmitter transporter,serotonin),member 4,SLC6A4]等,它们可能通过9个相关途径和69个生物学过程发挥作用,其中包括钙信号通路、唾液分泌等。体内实验发现,SZS生用、炒用及生炒合用均能减少小鼠活动性,增强戊巴比妥钠催眠效果,降低皮质及海马中ACHE、ADRA1B和SLC6A4 mRNA水平,调节血浆中乙酰胆碱、肾上腺素等含量,且效果与药物剂量呈正比。结论SZS具有镇静催眠作用,以高剂量的生炒SZS合煎液效果更佳,这种作用可能是由影响神经递质及其相关受体水平,介导中枢神经系统导致的。Aim To explore the differences in sedative and hypnotic effects of Semen Ziziphi Spinosae(SZS)before and after processing based on network pharmacology and animal experiments.Methods The chemical components and corresponding targets of SZS were collected through relevant platforms and databases,the insomnia and sleep disorder targets were retrieved,and the intersection targets of drugs and diseases were obtained.The protein interaction relationships were constructed,and the Chinese medicinal herb-component-target-pathway network was drawn.Then database was used to analyze pathway enrichment.Based on the predicted results,the effects of different SZS products on Kunming mice were evaluated through pentobarbital induced sleep test,behavioral analysis,brain tissue related gene mRNA levels,and plasma neurotransmitters.Results The target genes related to SZS and insomnia were acetylcholinesterase(ACHE),alpha-1B adrenergic receptor(ADRA1B),solute carrier family 6(neurotransmitter transporter,serotonin),member 4(SLC6A4),which might play a role through 9 related pathways and 69 biological processes such as calcium signaling pathway,salivary secretion,and so on.In vivo experiments found that SZS could reduce mouse activity,enhance the hypnotic effect of pentobarbital sodium,lower the levels of ACEE,ADRA1B,and SLC6A4 mRNA in cortex and hippocampus,and regulate the levels of acetylcholine,adrenaline,and other substances in plasma,all of which could be used in combination with raw and fried methods.The effect was proportional to the dosage of the drug.Conclusions SZS has sedative and hypnotic effects,and high doses of crude and parched SZS combined decoction have better effects.This effect may be caused by affecting the levels of neurotransmitters and their related receptors,mediating the central nervous system.

关 键 词：酸枣仁 炮制 网络药理学 失眠 镇静 催眠 

分 类 号：R-332[医药卫生] R282.71R322.8R319R741R971.3