基于肠道菌群研究天王补心丹通过调控单胺代谢治疗失眠的作用及机制  

Effects and mechanism of Tianwang Buxin Dan on insomnia by regulating monoamine metabolism through intestinal flora

作　　者：杨文育 李云海 唐飞越 徐泽丽 叶星兰 王平 杨希茜 YANG Wenyu;LI Yunhai;TANG Feiyue;XU Zeli;YE Xinglan;WANG Ping;YANG Xiqian(Clinical College of Traditional Chinese Medicine,Hubei University of Chinese Medicine,Wuhan 430000,China;Huanggang Polytechnic College,Huanggang 438002,China;Institute of Gerontology,Hubei University of Chinese Medicine,Wuhan 430000,China)

机构地区：[1]湖北中医药大学中医临床学院,武汉430000 [2]黄冈职业技术学院,黄冈438002 [3]湖北中医药大学老年医学研究所,武汉430000

出　　处：《中华中医药杂志》2025年第3期1392-1396,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：湖北省中医药管理局中医药重点学科项目(No.5432-10100204);湖北省教育厅科学研究计划项目(No.B2022123);中医药传承与创新“百千万”人才工程(岐黄工程)一一国家中医药领军人才支持计划(No.国中医药人教发【2018】12号)。

摘　　要：目的:探讨天王补心丹通过肠道菌群调控单胺代谢治疗失眠的作用及机制。方法:采用DL-4-氯苯氨酸(PCPA)构建失眠模型无菌大鼠,分别应用天王补心丹、地西泮等对失眠大鼠进行干预,采用旷场实验对失眠大鼠的行为学进行评价,并观察天王补心丹对其整体状态、体质量、潜伏期睡眠时间和持续睡眠时间的影响。采用ELISA测定额叶皮层中5-羟色胺(5-HT)、5-羟基吲哚-乙酸(5-HIAA)、去甲肾上腺素(NE)及多巴胺(DA)含量变化。采用粪菌移植法进一步验证。结果:与对照组比较,模型组大鼠出现一定程度上的倦急懒动,对刺激反应性下降,潜伏期睡眠时间增加(P<0.01),持续睡眠时间减少(P<0.01),旷场实验相关检测指标下降(P<0.01),5-HT、5-HIAA、NE及DA的含量降低(P<0.01),而给予天王补心丹或地西泮干预后,上述情况得到逆转。粪菌移植法结果显示,与对照组比较,模型粪菌组睡眠潜伏期增加(P<0.01),大鼠活动减少,大便较稀软,持续睡眠时间减少(P<0.01),大鼠总路程、直立次数、毛发梳理次数及5-HT、5-HIAA、NE及DA的含量均明显降低(P<0.01)。与模型粪菌组比较,天王补心丹粪菌组和模型粪菌+天王补心丹组大鼠整体状态有所好转。结论:天王补心丹能够通过肠道菌群调控额叶皮层的单胺代谢,从而缓解大鼠的失眠症状。Objective:To explore the effects and mechanism of Tianwang Buxin Dan in treating insomnia by regulating monoamine metabolism through intestinal flora.Methods:PCPA was used to construct sterile rats with insomnia model,and Tianwang Buxin Dan and diazepam were respectively applied to intervene the insomnia rats.Open field experiment was used to evaluate the behavior of the insomnia rats,and the effects of Tianwang Buxin Dan on their overall state,body weight,latent sleep time and continuous sleep time were observed.The contents of 5-HT,5-HIAA,NE and DA in frontal cortex were determined by ELISA.Further validation was conducted using the fecal microbiota transplantation method.Results:Compared with the control group,the rats in the model group showed a certain degree of slugginess,decreased responsiveness to stimulation,increased sleep latency(P<0.01),decreased continuous sleep time(P<0.01),decreased relevant detection indexes in open field experiment(P<0.01),and decreased contents of 5-HT,5-HIAA,NE and DA(P<0.01).However,after the intervention of Tianwang Buxin Dan or diazepam,the above situation was reversed.Compared with the control group,the sleep latency of the model fecal bacteria group increased(P<0.01),the activity of the rats decreased,the stool was softer,the sleep duration decreased(P<0.01),the total distance of the rats,the number of upright,the number of hair grooming and the contents of 5-HT,5-HIAA,NE and DA decreased significantly(P<0.01).Compared with the model coprobacteria group,the overall state of rats in the Tianwang Buxin Dan coprobacteria group and the model coprobacteria+Tianwang Buxin Dan group was improved.Conclusion:Tianwang Buxin Dan can regulate monoamine metabolism in frontal cortex through intestinal fora,thus alleviating insomnia symptoms in rats.

关 键 词：天王补心丹 失眠 单胺代谢 肠道菌群 5-羟色胺 5-羟基吲哚-乙酸 

分 类 号：R285.5[医药卫生—中药学]