左归丸、右归丸对失眠和多睡模型大鼠血浆中单胺类神经递质的影响

Impact of Zuogui Wan(左归丸) and Yougui Wan(右归丸) on Plasma Monoamine Neurotransmitter in Insomnia and Sleepiness Model Rats'

目的探讨左归丸、右归丸改善睡眠失衡状态的可能作用机制。方法 25只SD大鼠随机分为正常对照组、失眠模型组、多睡模型组、左归丸组、右归丸组,每组5只。失眠模型组和左归丸组大鼠给予中缝背核内微量注射1A型5-羟色胺(5-HT1A)受体阻断剂WAY 100635建立失眠模型,多睡模型组和右归丸模型组大鼠微量注射5-HT1A受体激动剂8-OH-DPAT建立多睡模型,正常对照组中缝背核微量注射等量的生理盐水,连续3天。于末次注射2h后左归丸组大鼠给予左归丸溶液17.5 g/(kg·d)灌胃,右归丸组给予右归丸溶液18.5 g/(kg·d)灌胃,其余3组大鼠给予10 ml/(kg·d)蒸馏水灌胃,每天1次,共7天。采用高效液相谱法检测各组大鼠血浆中单胺类神经递质多巴胺(DA)、二羟基苯乙酸(DOPAC)、5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA)的含量,并计算5-HIAA/5-HT。结果与正常对照组比较,失眠模型组大鼠血浆DA、DOPAC、5-HIAA含量及5-HIAA/5-HT升高(P<0.01);多睡模型组大鼠血浆DA、DOPAC、5-HIAA含量及5-HIAA/5-HT降低(P<0.05或P<0.01)。与失眠模型组比较,左归丸组大鼠血浆DA、DOPAC、5-HIAA含量及5-HIAA/5-HT均降低(P<0.05或P<0.01);与多睡模型组比较,右归丸组大鼠血浆DA、DOPAC、5-HIAA含量及5-HIAA/5-HT升高(P<0.05)。各组大鼠血浆5-HT含量差异均无统计学意义(P>0.05)。结论左归丸能有效降低失眠大鼠兴奋性神经递质,右归丸能有效升高多睡大鼠兴奋性神经递质,二者可能通过平衡神经递质改善睡眠失衡状态。

Objective To explore the potential mechanism of Zuogui Wan（左归丸） and Yougui Wan（右归丸） in improving sleep imbalance. Methods Twenty-five Sprague Dawley（SD） rats were randomized into the normal control group,the insomnia model group,the sleepiness model group,the Zuogui Wan group and the Yougui Wan group,with 5 rats in each group. Rats in the insomnia model group and the Zuogui Wan group were made insomnia models by type 1 A 5-hydroxytryptamine（5-HT1 A） receptor blocker WAY 100635 microinjection into dorsal raphe nucleus. Rats in the sleepiness model group and the Yougui Wan group were made sleepiness models by 5-HT1 A receptor agonist 8-OH-DPAT microinjection. The normal control group was given equivalent normal saline microinjection into dorsal raphe nucleus,for 3 days. Two hours after the last injection,rats in the Zuogui Wan group was given Zuogui Wan solution 17. 5 g/（kg · d） by gavage. The Yougui Wan group was given Yougui Wan solution 18. 5 g/（kg·d） by gavage. Rats in the other 3 groups were given 10 ml/（kg·d） distilled water by gavage,once every day,for 7 days. The levels of monoamine neurotransmitter dopamine（DA）,dihydroxyphenylacetic acid（DOPAC）,5-hydroxytryptamine（5-HT） and 5-hydroxyindoleacetic acid（5-HIAA） in rats＇ plasma in each group were determined by high performance liquid spectrum method; 5-HIAA/5-HT was calculated. Results Compared with the normal control group,the levels of plasma DA,DOPAC and 5-HIAA as well as 5-HIAA/5-HT in the insomnia model group increased（P〈0. 01）; while those in the sleepiness model group decreased（P〈0. 05 or P〈0. 01）. Compared with the insomnia model group,the levels of DA,DOPAC and 5-HIAA as well as 5-HIAA/5-HT in the Zuogui Wan group decreased（P〈0. 05 or P〈0. 01）. Compared with the sleepiness model group,the levels of DA,DOPAC and5-HIAA as well as 5-HIAA/5-HT in the Yougui Wan group increased（P〈0. 01）. The difference of 5-HT level in rats＇ plasma in each group was not significant（P〈0. 05）. Conclusion Zuogui Wan might reduce the excitatory neurotransmitters in insomnia rats,while Yougui Wan might increase the excitatory neurotransmitters in sleepiness rats. Both might improve sleep imbalance by balancing neurotransmitters.