五味子藤茎木脂素对小鼠镇静催眠及抗焦虑作用研究

Sedative,Hypnotic and Anti-anxiety Effects of Lignans from Schisandra chinensis Vine Stem in Mice

目的:研究五味子藤茎木脂素(Schisandra chinensis vine stem lignans,SSL)的镇静、抗焦虑及催眠作用并初步探讨其作用机制。方法:将150只ICR雄性小鼠平均随机分为5组,分别为空白对照组、SSL低、中、高剂量组和地西泮阳性对照组。采用灌胃给药,每次0.1 mL/10 g,每天一次,连续7 d。应用小鼠自主活动实验观察镇静效果;应用高架十字迷宫、高架零迷宫实验观察抗焦虑作用;通过戊巴比妥钠协同睡眠实验观察催眠作用;用酶联免疫吸附法检测小鼠脑组织中γ-氨基丁酸(γ-aminobutyric acid,GABA)、谷氨酸(glutamate,Glu)含量。应用Western blot方法检测小鼠脑组织中GABAAα1表达水平。结果:与对照组比,各剂量SSL显著减少小鼠站立次数和活动次数(P<0.01);中、高剂量SSL显著增加小鼠进入开放臂次数(open arm entry,OE),开放臂停留时间(open arm time,OT)和开放探头次数(open arm probe,OP)(P<0.05或P<0.01);各剂量SSL均增加阈下剂量戊巴比妥钠诱导小鼠睡眠只数,显著延长阈剂量戊巴比妥钠诱导的小鼠睡眠时间(P<0.05或P<0.01),缩短小鼠睡眠潜伏期(P<0.01);各剂量SSL组小鼠脑组织中GABA含量极显著增加(P<0.01),而中、高剂量SSL组小鼠脑组织中Glu含量极显著降低(P<0.01),GABA/Glu极显著增加(P<0.01)。高剂量SSL组小鼠脑组织中GABAAα1蛋白表达极显著增加(P<0.01)。结论:SSL对小鼠具有镇静、催眠及抗焦虑作用,其机制可能与其调节其脑组织中GABA及Glu含量及GABAAα1受体表达水平有关。

Objective:To study thesedative,anti-anxiety and hypnotic effects of Schisandra chinensis vine stem lignans(SSL)and its underlying mechanism.Methods:One hundred and fifty ICR male mice were evenly and randomly divided into 5 groups,namely the blank control group,the SSL low-dose group(35 mg/kg),middle-dose group(70 mg/kg),and high-dose group(140 mg/kg),and diazepam positive control group(4 mg/kg).All treatments were administered intragastrically,0.1 mL/10 g and once daily for 7 days.The autonomous activities of mice were used to observe the sedative effect,the elevated plus maze and elevated zero Maze were used to observe the anti-anxiety effect.The synergistic sleep test of pentobarbital sodium at subthreshold and threshold doses was used to observe the hypnotic effect.Enzyme-linked immunosorbent assay(ELISA)was used to detect the content ofγ-aminobutyric acid(GABA)and glutamate(Glu)in mouse brain tissue.Results:In comparison to the blank control group,the numbers of standing and spontaneous activities of the mice was significantly reduced(P<0.01)in all SSL groups.The open arm time,the numbers of open arm entry and open arm probe significantly increased(P<0.05 or P<0.01)in SSL middle-and high-dose groups.The number of sleep mice under the subthreshold dose of pentobarbital sodium increased in all SSL groups,the sleep latency was shortened and sleep time increased in mice under the threshold dose of pentobarbital sodium in all SSL groups(P<0.05 or P<0.01).The content of GABA in brain tissue significantly increased(P<0.01)in all SSL groups,while Glu content significantly decreased(P<0.01)and GABA/Glu ratio significantly increased(P<0.01)in SSL middle-and high-dose groups,and the expression of GABAAα1 protein in brain tissue of mice significantly increased(P<0.01)in SSL high-dose group.Conclusion:SSL had sedative,hypnotic and anti-anxiety effects in mice,the mechanism might be related to the regulation of GABA content in the brain tissue.