五味子醋镇静催眠抗焦虑作用及其作用机制

Sedative,Hypnotic and Anxiolytic Effect and Mechanism of Schisandrae Chinensis Fructus Vinegar

目的：观察五味子醋（Schisandrae Chinensis Fructus Vinegar,SV）的镇静催眠抗焦虑作用并初步探讨其作用机制。方法：将50只ICR雄性小鼠随机分为正常组、地西泮组（镇静实验剂量为2 mg·kg^-1,催眠及抗焦虑实验剂量为4 mg·kg^-1）和SV低、中、高剂量组（灌胃给予相应剂量SV）。各组连续灌胃给药7 d后,采用自主活动记录仪观察SV对小鼠自主活动的影响;通过阈下剂量戊巴比妥钠协同睡眠实验观察SV对小鼠睡眠只数、潜伏期及睡眠时间的影响。采用高架十字迷宫（elevated plus maze,EPM）检测SV的抗焦虑作用;采用酶联免疫吸附实验（ELISA）检测SV对小鼠脑组织中γ-氨基丁酸（γ-aminobutyricacid,GABA）及谷氨酸（glutamate,Glu）含量的影响;应用蛋白免疫印迹法（Western blot）检测SV对小鼠脑组织中GABAAα1及GABAAγ2表达的影响。结果：与正常组比较,SV中、高剂量组小鼠自主活动次数明显减少（P〈0.05,P〈0.01）,协同阈下剂量戊巴比妥钠诱导小鼠睡眠只数增加;协同阈剂量戊巴比妥钠诱导的小鼠睡眠潜伏期明显缩短、睡眠时间显著延长（P〈0.05,P〈0.01）,EPM模型小鼠开臂/在臂滞留时间率（OT）和开臂/在臂进入次数比率（OE%）明显增加（P〈0.05）;SV高剂量组小鼠脑组织中GABA含量显著增加（P〈0.01）,Glu含量显著减少（P〈0.01）;SV中、高剂量组小鼠脑组织中GABAAα1和GABAAγ2蛋白表达明显增加（P〈0.05,P〈0.01）。结论：SV具有镇静、催眠及抗焦虑作用,该作用与其调节小鼠脑组织中GABA,Glu含量及GABAAα1,GABAAγ2蛋白表达有关。

Objective： To observe the sedative,hypnotic and anxiolytic effects of Schisandrae Chinensis Fructus vinegar(SV） and explore its underlying mechanisms. Method： Fifty ICR male mice were randomly divided into blank control group(gavage distilled water,at a dose of 10 m L·kg-1）,diazepam group(sedative experimental dose of 2 mg·kg^-1,hypnosis and anti-anxiety experiment dose of 4 mg·kg^-1）,low-dose SV group,medium-dose SV group and high-dose SV group(corresponding doses by intragastric administration）, for consecutive 7 days. The effect of SV on the locomotor activity of mice was observed with locomotor activity recorder. By using the synergistic sleeping experiment with SV and threshold-dose pentobarbital sodium,the effect of SV on the number of sleeping mice,the sleeping latency and sleeping time were observed. The anxiolytic effect of SV was observed by using elevated plus maze(EPM）. The effects of SV on the contents of γ-aminobutyric acid(GABA） and glutamate(Glu） were observed by enzyme-linked immunosorbent assay(ELISA）,and Western blot was used to observe the effect of SV on the expression levels of GABAAα1 and GABAAγ2 in the brain tissues. Result：As compared with those in the blank control group,the number of locomotor activities(P〈0. 05,P〈0. 01）; the number of sleeping mice was increased significantly(P〈0. 05）; the sleeping latency was significantly shortened and the sleeping time was significantly prolonged in the medium-dose and high-dose SV groups(P〈0. 05）. The open-arms time percentage(OT） and open-arms entries percentage(OE） in EPM model mice were increased significantly in the medium-dose and high-dose SV groups(P〈0. 05）; the content of GABA was increased significantly(P〈0. 05） and the content of Glu was decreased significantly in the brain tissues in the high-dose SV group only(P〈0. 05）; the protein expression levels of GABAAα1 and GABAAγ2 were increased significantly in the medium-dose and high-dose SV groups(P〈0. 05,P〈0. 01）. Conclusion： SV has sedative,hypnotic and anxiolytic effects,and its mechanism may be related to the regulation of GABA and Glu contents as well as the protein expression of GABAAα1 and GABAAγ2 in brain tissues.