基于下丘脑-垂体-肾上腺轴对比杂交天麻及其亲本醇提物镇静催眠药效学研究  

Comparison sedative and hypnotic pharmacodynamics of hybrid Gastrodia elata and its parent alcohol extracts based on hypothalamic-pituitary-adrenal axis

作　　者：高翰博 王广政 巩晴晴 俞年军 方悦 杜方平 GAO Han-bo;WANG Guang-zheng;GONG Qing-qing;YU Nian-jun;FANG Yue;DU Fang-ping(College of Pharmacy,Anhui University of Chinese Medicine,Hefei 230012;Institute of Conservation and Development of Traditional Chinese Medicine Resources Academy of Traditional Chinese Medicine,Hefei 230012;Anhui Joint Key Laboratory of Functional Activity and Resource Utilization of Edible and Medicinal Fungi,Lu’an Anhui 237300;Anhui Collaborative Innovation Centre for Ouality Enhancement of Authentic Chinese Herbs,Hefei 230012;Key Laboratorv of Traditional Chinese Medicine Research and Development of Anhui,Hefei 230012;Jinzhai County Jinshanzhai Specialized Cooperative of Edible(Medicinal)Fungi Planting,Lu’an Anhui 237399)

机构地区：[1]安徽中医药大学药学院,合肥230012 [2]安徽省中医药科学院中药资源保护与开发研究所,合肥230012 [3]食药用菌功能活性与资源利用安徽省联合共建学科重点实验室,安徽六安237300 [4]省部共建安徽道地中药材品质提升协同创新中心,合肥230012 [5]中药研究与开发安徽省重点实验室,合肥230012 [6]金寨县金山寨食(药)用菌种植专业合作社,安徽六安237399

出　　处：《中南药学》2024年第4期871-877,共7页Central South Pharmacy

基　　金：省部共建安徽道地中药材品质提升协同创新中心项目(教科信厅函[2022]4号);直接口服中药饮片亳州市重点实验室开放基金(No.ZFYP20211204)。

摘　　要：目的 基于下丘脑-垂体-肾上腺轴(HPA轴)和单胺类神经递质水平研究比较杂交天麻及其亲本醇提物镇静催眠药效。方法 连续4 d对小鼠腹腔注射对氯苯丙氨酸(PCPA)造失眠模型,造模同期给药。以阳性药艾司唑仑、杂交天麻及其亲本(红天麻、乌天麻)醇提取物、天麻素给药,7 d后检测腹腔注射戊巴比妥钠诱导小鼠的睡眠发生率、睡眠潜伏期及睡眠时间;苏木精-伊红染色法(HE)染色观察小鼠大脑相关组织的病变,ELISA法检测机体中单胺类神经递质5-羟色胺(5-HT)、去甲肾上腺素(NE)、多巴胺(DA)含量水平及HPA轴激素及血清中γ-氨基丁酸(GABA)水平。结果 PCPA致失眠小鼠造模成功,各组天麻醇提取物均可改善失眠小鼠行为异常,缓解失眠小鼠脑组织病变,促进机体内5-HT、DA表达量的回调;抑制血清中NE水平及机体内促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)、皮质酮(CORT)水平升高,促进机体GABA水平提高。杂交天麻对单胺类神经递质的调节作用优于红天麻;抑制HPA轴亢奋与提升机体内GABA水平作用优于乌天麻。结论 杂交天麻及其亲本醇提物均可通过抑制HPA轴亢奋与调节机体内单胺类神经递质紊乱缓解失眠症状。杂交天麻综合疗效与亲本相近,可在后续药效学研究中提供数据以便参考。Objective To compare the sedative and hypnotic effects of hybrid Gastrodia elata Blume and its parent alcohol extract based on hypothalamic-pituitary-adrenal(HPA)axis and monoamine neurotransmitter levels.Methods The insomnia model was established by intraperitoneal injection of p-chlorophenylalanine(PCPA)in mice for four consecutive days,and the drug was administered at the same time.The positive drug estazolam,hybrid Gastrodia elata and its parent alcohol extract(Gastrodia elata BL.f.glauca and Gastrodia elata BL.f.elata),and gastrodin were administered.Seven days later,the sleep incidence,sleep latency,and sleep time of mice induced by intraperitoneal injection of sodium pentobarbital were detected.Hematoxylin eosin staining was used to observe the lesions of brain related tissues in mice.ELISA method was used to detect the levels of monoamine neurotransmitters serotonin,5-hydroxytryptamine(5-HT),norepinephrine(NE)and dopamine(DA)in the body.HPA axis hormones in the body and serumγ-aminobutyric acid(GABA)levels were also measured.Results The mice model of PCPA induced insomnia mice was successfully established.Gastrodia alcohol extract of each group improved the behavioral abnormalities in insomnia mice,alleviated the brain tissue lesions of insomnia mice,and promoted the callback of 5-HT and DA expression in the body;the increase of NE level in the serum,corticotropin releasing hormone(CRH),adrenocorticotropic hormone(ACTH)and corticosterone(CORT)levels in the body were inhibited,and GABA level increased in the body.The regulatory effect of hybrid Gastrodia elata on monoamine neurotransmitters was better than that of Gastrodia elata BL.f.elata.The effect of inhibiting HPA axis hyperactivity and increasing GABA level in the body was better than that of Gastrodia elata BL.f.glauca.Conclusion Both hybrid Gastrodia elata and its parent ethanol extract can alleviate insomnia by inhibiting HPA axis hyperactivity and regulating monoamine neurotransmitter disorders in the body.The comprehensive efficacy of hybrid Ga

关 键 词：杂交天麻 镇静催眠 药效差异 HPA轴 5-羟色胺 

分 类 号：R285[医药卫生—中药学]