沉香线香燃香调节多神经递质途径的抗焦虑/抑郁作用及机制  

The anti-anxiety/depression effect and mechanism of agarwood line incense burning on regulating multi-neurotransmitter pathways

作　　者：弓宝[1] 王灿红 吴玉兰 刘洋洋[1] 魏建和[1,3] GONG Bao;WANG Can-hong;WU Yu-lan;LIU Yang-yang;WEI Jian-he(Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine&Key Laboratory of State Administration of Traditional Chinese Medicine for Agarwood Sustainable Utilization,Hainan Branch of the Institute of Medicinal Plant Development,Chinese Academy of Medical Sciences and Peking Union Medical College,Haikou 570311,China;Maoming Branch,Guangdong Laboratory for Lingnan Modern Agriculture,Maoming 525099,China;Key Laboratory of Bioactive Substances and Resources Utilization Chinese Herbal Medicine,Ministry of Education&National Engineering Laboratory for Breeding of Endangered Medicinal Materials,Institute of Medicinal Plant Development,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100193,China)

机构地区：[1]中国医学科学院北京协和医学院药用植物研究所海南分所,海南省南药资源保护与开发重点实验室&国家中医药管理局沉香可持续利用重点研究室,海口570311 [2]岭南现代农业科学与技术广东省实验室茂名分中心,茂名525099 [3]中国医学科学院北京协和医学院药用植物研究所,中草药物质基础与资源利用教育部重点实验室&濒危药材繁育国家工程实验室,北京100193

出　　处：《中国新药杂志》2023年第13期1368-1376,共9页Chinese Journal of New Drugs

基　　金：国家自然科学基金青年基金项目(82204657);中国医学科学院医学与健康科技创新工程重大协同创新项目(2021-I2M-1-032);海南省重点研发计划项目(ZDYF2022SHFZ030);海南省科技厅海南省基础与应用基础研究计划(自然科学领域)高层次人才项目(2019RC345);茂名市科技计划项目(2022S032)。

摘　　要：目的:探讨沉香线香(ALI)对小鼠焦虑模型和抑郁模型的作用及其机制。方法:采用间氯苯哌嗪(MCPP)和慢性不可预知性温和刺激(CUMS)法分别制作小鼠焦虑和抑郁模型,观察熏香后模型动物旷场活动(OFT)、明暗箱穿梭(LDT)、悬尾(TST)、游泳(FST)等行为学变化;ELISA法测定海马组织中五羟色胺(5-HT)、谷氨酸(Glu)、伽马氨基丁酸A受体(GABAA)水平;Western Blot法检测颗粒体蛋白(GRN2B)、代谢型谷氨酸受体5抗体(GRM5)、谷氨酸受体1(GluR1)及囊泡谷氨酸转运蛋白1(VGluT1)表达。结果:ALI可降低焦虑模型动物总活动路程和速度(P<0.05),增加静止时间(P<0.05),降低在暗箱中活动路程和速度(P<0.05);增加抑郁模型动物总路程和速度(P<0.05),降低静止时间(P<0.05)和强迫游泳及悬尾不动时间(P<0.05);与焦虑模型组比较,中、高剂量组的GLu水平降低(P<0.05),而GABAA,5-HT水平升高(P<0.05);与抑郁模型组比较,中、高剂量组5-HT和GLu水平升高(P<0.05),GABAA水平降低(P<0.05);ALI熏香吸入能提高焦虑模型动物GRN2B,GRM5,GluR1,VGluT1蛋白表达;可提高抑郁模型动物GRN2B,GluR1,VGluT1蛋白表达,降低GRM5蛋白表达。结论:ALI对焦虑模型和抑郁模型的行为均有改善,其作用机制可能与调控5-HT,GABAA,Glu神经递质水平和影响GRN2B,GRM5,GluR1,VGluT1的蛋白表达有关。Objective:To investigate the effect of agarwood line incense(ALI) burning on anxiety and depression and its mechanism.Methods:Chronic unforeseeable mild stress(CUMS) was applied to induce depression-like model and M-chloropheniperazine(MCPP) was applied to induce anxiety model.By using open field test(OFT),light-dark transtition test(LDT),tail suspension test(TST) and forced swim test(FST),changes of activity after inhaling the incense were measured to evaluate its effects of anti-anxiety and anti-depression.To investigate the mechanism,monoamine neurotransmitters in brain,such as 5-HT,Glu,and GABAA,were observed by ELISA.The protein expression levels of GRN2B,GRM5,GluR1,VGluT1 were evaluated by Western Blot.Results:Compared with the anxiety model group,the total distance and average velocity significantly reduced(P<0.05),the rest time increased(P<0.05),and the distance and average velocity in the black box reduced(P<0.05) in ALI inhalation group.Compared with the depression model group,the total distance and average velocity significantly increased(P<0.05),the rest time decreased(P<0.05),and the immobile time of TST and FST decreased(P<0.05) in the ALI group.The ALI inhalation increased the levels of 5-HT and GABA(P<0.05),decreased the level of Glu(P<0.05) in the brain tissues of the anxiety model group.ALI decreased the level of GABA(P<0.05),and increased the levels of 5-HT and Glu(P<0.05).ALI increased the protein expression levels of GRN2B,GRM5,GluR1,and VGluT1 in hypothalamus of the rats in anxiety model group.ALI decreased the protein expression of GRM5 and increased the protein expressions of GRN2B,GluR1,and VGluT1 in hypothalamus of the rats in depression model group.Conclusion:ALI has a significant anxiolytic and anti-depression effects,and the mechanism may be related to the regulation of the levels of 5-HT,Glu,GABAA,and the protein expression of GRN2B,GluR1,and VGluT1 in hypothalamus.

关 键 词：沉香线香 燃香 抗抑郁 抗焦虑 多神经递质 

分 类 号：R965[医药卫生—药理学]