中医五行音乐结合药物对焦虑模型大鼠行为及海马神经递质兴奋/抑制平衡系统的影响

Effects of TCM five-element theory and medicines on the behavior and hippocampal neurotransmitter/inhibitory balance system in the anxiety rat model

目的通过对焦虑模型大鼠的行为学及海马神经递质兴奋/抑制平衡系统的影响,探讨在传统中医理论指导下,音乐疗法对焦虑症的疗效与作用机制。方法将50只SD大鼠按体重随机分为正常组、模型组、对照组、音乐治疗组和联合治疗组,每组10只。除正常组外,其余组别大鼠采用随机慢性情绪刺激复制焦虑症大鼠模型,各组在造模的同时均进行治疗,对照组灌胃地西泮2.5 mg/kg,灌胃量为10 ml/kg;正常组和模型组大鼠等量灌胃生理盐水;音乐治疗组则将大鼠放入一安静避光的空间,播放五行音乐中的宫调与羽调音乐;联合治疗组则同时灌胃地西泮+五行音乐治疗,具体方法与对照组和音乐治疗组相同。以高架十字迷宫实验和旷场试验观察中医五行音乐对焦虑症大鼠行为[开放臂次数(OE)、开放臂滞留时间(OT)和水平、垂直运动次数]的影响,测定大鼠脑内5-羟色胺(5-HT)、去甲肾上腺素(NE)、多巴胺(DA)及γ-氨基丁酸(GABA)含量;RT-PCR法检测海马组织中GABA mRNA的表达。结果与正常组比较,模型组大鼠从第7天开始,OE、OT、水平和垂直运动次数均显著下降(P<0.05,P<0.01)。与模型组比较,对照组、音乐治疗组和联合治疗组的OE、OT、水平和垂直运动次数均显著增大(P<0.05,P<0.01);同时显著减少焦虑症大鼠脑内5-HT、NE和DA含量(P<0.05),增加脑内GABA含量(P<0.01)。RT-PCR结果显示,与正常组比较,模型组大鼠海马组织中GABA mRNA的相对表达量显著降低(P<0.01);与模型组比较,对照组、音乐治疗组和联合治疗组GABA mRNA的相对表达量均显著升高,差异有统计学意义(P<0.01)。结论中医五行音乐治疗对焦虑症有一定治疗效果,其治疗机制可能通过影响海马神经递质兴奋/抑制平衡系统,与地西泮相比治疗效果略差,而两者联合应用治疗的效果最佳,提示在使用中医五行音乐治疗焦虑症时,仍需结合药物进行治疗。

Objective To explore the effects and the mechanism of music theory under the guide of traditional Chinese medicine theory through the influence on the behavior and hippocampal neurotransmitter/inhibitory balance system in the anxiety rat model.Methods A total of 50 SD rats were randomized into a normal group,a model group,a control group,a music therapy group and a combined therapy group according to the body weight,10 rats in each one.Except the normal group,the random chronic emotional stimulation was adopted in the rest groups to duplicate anxiety rat model.Simultaneously,the corresponding treatment was given.In the control group,the lavage was given with diazepam 2.5mg/kg,and the volume was 10ml/kg.In the normal group and the model group,the physical saline of the same volume was used in lavage.In the music therapy group,the rats were put in a quiet and lightless place in which the gong-tone and yu-tong music of five elements was played.In the combined therapy group,the lavage with diazepam and five-element music therapy was applied.The concrete method was same as the control group and the music therapy group.The elevated maze test and the open-field test were adopted to assess the effects on the rat behaviors[open arm entry（OE）,open arm retention time（OT）and the frequency of the horizontal and vertical movement].The expressions of 5-HT,NE,DA and GABA were determined.RT-PCR method was adopted to determine the expression of GABM mRNA in the hippocampal tissue.Results Compared with the normal group,since the Day 7,OE,OT and the frequency of the horizontal and vertical movement were reduced significantly in the model group（P 〈 0.05,P 〈 0.01）.Compared with the model group,OE,OT and the frequency of the horizontal and vertical movement were increased significantly in the control group,the music therapy group and the combined therapy group（P 〈 0.05,P 〈 0.01）.Simultaneously,the contents of 5-HT,NE and DA in the brain were reduced significantly in the anxiety rats（P 〈 0.05）and GABA increased（P 〈 0.01）.The RT-PCR results showed that compared with the normal group,the relevant expression of hippocampal GABA mRNA was reduced significantly in the model group（P 〈 0.01）.Compared with the model group,the relevant expressions of GABA mRNA in the control group,the music therapy and the combined therapy group were increased significantly,indicating the significant differences（P 〈 0.01）.Conclusion The five-element music treatment achieves a certain effect on anxiety.This mechanism is possibly related to the impacts on hippocampal neurotransmitter/inhibitory balance system.The therapeutic effect is inferior to that of diazepam.But the combination of music therapy and medicine achieves the optimal effects.It is suggested that medication should be used together with the music therapy in the treatment of anxiety.