刺五加根皮乙醇提取物和短梗五加根皮乙醇提取物对小鼠的镇静催眠作用及其机制

doi:10.13481/j.1671-587x.20200504

摘要/Abstract

摘要： 目的：对比刺五加根皮乙醇提取物（SENR）和短梗五加根皮乙醇提取物（SESR）的镇静催眠作用及其作用机制，探讨短梗五加根皮替代刺五加根皮的可行性。方法：根据测定指标的不同，选择雄性昆明小鼠360只，每120只随机分为空白对照组，地西泮组（DZP，3 mg·kg^-1，灌胃给药），不同剂量（4、8、16、32和64 mg·kg^-1）SENR组和不同剂量（4、8、16、32和64 mg·kg^-1）SESR组，每组10只，连续给药5 d，记录各组小鼠自主活动次数；利用亚催眠剂量（28 mg·kg^-1）戊巴比妥钠诱导睡眠实验记录小鼠睡眠发生率，利用催眠剂量（48 mg·kg^-1）戊巴比妥钠诱导睡眠实验记录小鼠睡眠潜伏期和睡眠时间，筛选出SENR和SESR的亚催眠剂量和催眠剂量。根据模型药[5-羟色氨酸（5-HTP）和氟马西尼（FLU）]的不同，雄性ICR小鼠180只，每60只随机分为空白对照组、模型对照组、SENR组、SESR组、SENR+模型药组和SESR+模型药组，每组10只，连续给药5 d，采用戊巴比妥钠诱导睡眠实验记录各组小鼠的睡眠发生率、睡眠潜伏期和睡眠时间，采用ELISA法测定小鼠脑组织中5-羟色胺（5-HT）和γ-氨基丁酸（GABA）水平。结果：与空白对照组比较，DZP组、不同剂量（8、16、32和64 mg·kg^-1）SENR组和不同剂量（8、16、32和64 mg·kg^-1）SESR组小鼠自主活动次数明显减少（P<0.05或P<0.01），睡眠发生率增加，睡眠潜伏期缩短且睡眠时间延长（P<0.05或P<0.01）；依据实验结果，选择SENR和SESR的亚催眠剂量为4 mg·kg^-1，催眠剂量为32 mg·kg^-1。5-HTP模型实验，与空白对照组、SENR（4 mg·kg^-1）组和SESR（4 mg·kg^-1）组比较，SENR+5-HTP组和SESR+5-HTP组小鼠睡眠发生率增加，睡眠潜伏期缩短（P<0.01），睡眠时间延长（P<0.01），脑组织中5-HT水平升高（P<0.01）；FLU模型实验，与空白对照组比较，SENR（32 mg·kg^-1）组和SESR（32 mg·kg^-1）组小鼠睡眠潜伏期缩短（P<0.01），睡眠时间延长（P<0.01）；与SENR（32 mg·kg^-1）组和SESR（32 mg·kg^-1）组比较，SENR+FLU组和SESR+FLU组小鼠睡眠潜伏期延长（P<0.01），睡眠时间缩短（P<0.01），脑组织中GABA水平降低（P<0.05）。结论：SENR和SESR均具有镇静催眠作用，其作用机制与上调脑组织中5-HT和GABA水平有关；在镇静催眠方面，短梗五加根皮可作为刺五加根皮的替代品。

关键词: 刺五加, 短梗五加, 根皮, 镇静, 催眠, 乙醇提取物

Abstract: Objective: To compare the sedative and hypnotic effects of ethanol extract of Acanthopanax senticosus root bark (SENR) and ethanol extract of Acanthopanax sessiliflorus root bark (SESR) and their mechanisms, and to explore the feasibility of replacing Acanthopanax senticosus root bark with Acanthopanax sessiliflorus root bark. Methods: According to the different detection indexes, every 120 of 360 male Kunming mice were randomly divided into blank control group, diazepam group (administrated with 3 mg·kg^-1 DZP by gavage), different doses (4, 8, 16, 32 and 64 mg·kg^-1) of SENR groups and different doses (4, 8, 16, 32 and 64 mg·kg^-1) of SESR groups;there were 10 mice in each group. The mice were administrated for 5 d continuously, and the number of locomotor activities of the mice in various groups were recorded. The sub-hypnotic dose (28 mg·kg^-1) of pentobarbital sodium-induced sleep experiment was used to record the incidence of sleep of the mice, and the hypnotic dose (48 mg·kg^-1) of pentobarbital sodium-induced sleep experiment was used to record the sleep latencies and sleep time of the mice. The hypnotic doses and sub-hypnotic doses of SENR and SESR were screened out according to the above experimental results. According to the different model drugs[5-hydroxytryptophan (5-HTP) and flumazenil (FLU)], every 60 of 180 male Kunming mice were randomly divided into blank control group, model control group, SENR group, SESR group, SENR + model drug group and SESR + model drug group;there were 10 mice in each group. The mice were administrated for 5 d continuously, and pentobarbital sodium-induced sleep experiment was used to record the incidence of sleep latencies and sleep time of the mice in various groups, and the 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA) levels in brain tissue of the mice were detected by ELISA. Results: Compared with blank control group, the number of locomotor activities of the mice in DZP group, different doses (8, 16, 32 and 64 mg·kg^-1) of SENR and different doses(8,16,32 and 64 mg·kg^-1) of SESR groups was decreased(P<0.05 or P<0.01), the incidence of sleep was increased, the sleep latencies were shortened and the sleep time was prolonged (P<0.05 or P<0.01). Based on the experimental results, the sub-hypnotic doses of SENR and SESR were selected to be 4 mg·kg^-1 and the hypnotic doses were 32 mg·kg^-1. In the 5-HTP model test, compared with blank control group and SENR (4 mg·kg^-1) group and SESR (4 mg·kg^-1) group, the incidences of sleep of the mice in SENR + 5-HTP group and co-administered SESR + 5-HTP group were increased, the sleep latencies were shortened(P<0.01), the sleep time was prolonged(P<0.01), and the levels of 5-HT in the brain tissue were increased (P<0.01). In the FLU model test, compared with blank control group, the sleep latencies of the mice in SENR (32 mg·kg^-1) group and SESR (32 mg·kg^-1) group were shortened(P<0.01) and the sleep time was prolonged (P<0.01). Compared with SENR (32 mg·kg^-1) group and SESR (32 mg·kg^-1) group, the sleep latencies of mice in SENR + FLU group and SESR + FLU group were prolonged(P <0.01), the sleep time was shortened(P <0.01), and the GABA levels in the brain tissue were decreased (P <0.05). Conclusion: Both of SENR and SESR can exhibit the sedative and hypnotic effects in the mice, and their mechanisms may be related to up-regulating the levels of 5-HT and GABA in the brain tissue; in terms of sedative and hypnotic effects, Acanthopanax sessiliflorus root bark could be used as a substitute for Acanthopanax senticosus root bark.

Key words: Acanthopanax senticosus, Acanthopanax sessiliflorus, root bark, sedation, hypnosis, ethanol extract

中图分类号:

R285

芮施, 赵岩, 王晶瑶, 蔡恩博, 祝洪艳, 李平亚, 刘金平. 刺五加根皮乙醇提取物和短梗五加根皮乙醇提取物对小鼠的镇静催眠作用及其机制[J]. 吉林大学学报(医学版), 2020, 46(05): 917-924.

RUI Shi, ZHAO Yan, WANG Jingyao, CAI Enbo, ZHU Hongyan, LI Pingya, LIU Jinping. Sedative and hypnotic effects of ethanol extracts of Acanthopanax senticosus root bark and Acanthopanax sessiliflorus root bark and their mechanisms[J]. Journal of Jilin University(Medicine Edition), 2020, 46(05): 917-924.

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