交泰丸对心肾不交型失眠大鼠中枢及外周神经递质的调控作用

为了探讨心肾不交型失眠的发病机制和交泰丸的调控作用,该实验对失眠模型大鼠及交泰丸治疗后大鼠中枢及外周9种神经递质变化进行了考察。大鼠腹腔注射对氯苯丙氨酸(PCPA, 400 mg·kg^-1·d^-1)复制心肾不交型失眠模型,灌胃给予交泰丸(3.3 g·kg^-1·d^-1)7 d后,采用UPLC-MS/MS技术并结合PCA分析方法对大鼠血清、尿液以及脑、心、肝、肾和肾上腺等组织中9种神经递质的含量和分布情况进行分析。结果显示,失眠大鼠血小板5-HT和5-HIAA比值较正常组明显下降,交泰丸对其具有明显的回调作用;和正常组相比,失眠大鼠血清中变化显著的神经递质有5-HIAA,E,NE,DA,Glu,ACH,而尿液中除ACH外,其他7种神经递质变化均较为显著,交泰丸对其也有回调作用;和正常组相比,除了HVA外失眠大鼠组织中8种神经递质都发生了变化,交泰丸对组织中神经递质均有调控作用,尤其是脑、肝和肾上腺。以上结果表明,失眠不仅脑组织中神经递质发生变化,外周组织中的递质也发生了一系列的变化,说明失眠是递质的系统失调,交泰丸在调控中枢神经系统的同时,对其他器官组织也具有一定的保护作用,体现了交泰丸治疗失眠多靶点和系统性的作用。

Regulatory effect of Jiaotai Pills on central and peripheral neurotransmitters in rats with heart-kidney imbalance insomnia

To explore the pathogenesis of heart and kidney imbalance insomnia and the regulatory effect of Jiaotai Pills,in order to study the changes of central and peripheral neurotransmitters in rat.Insomnia rats with heart and kidney imbalance were induced through intraperitoneal injection with p-chlorophenylalanine(PCPA,400 mg·kg-1·d-1),and the model rats were intragastrically administrated with Jiaotai Pills(3.3 g·kg-1·d-1)for 7 days.Nine neurotransmitters were determined by UPLC-MS/MS and principal component analysis(PCA)method in serum,urine,brain,heart,liver,kidney and adrenal gland of rats.The results showed that the ratio of 5-HT and 5-HIAA in platelet of insomnia rats was significantly lower than that in the normal group,and Jiaotai Pills had a significant up-regulatory or down-regulatory effect.Compared with the normal group,the changed neurotransmitters in blood of insomnia rats were 5-HIAA,E,NE,DA,Glu and ACH,and except ACH,the changes of 7 kinds of neurotransmitters in urine were more significant,Jiaotai Pills had a significant up-regulatory or down-regulatory effect.Compared with the normal group,all of the 8 neurotransmitters in insomnia rats except HVA were changed.Jiaotai Pills could regulate the neurotransmitters in each tissue of insomnia rats,especially in brain,liver and adrenal gland.In conclusion,insomnia is caused by not only a change of neurotransmitters in brain,but also a series of changes in peripheral tissues.It indicates that insomnia is a systematic imbalance of neurotransmitters.Jiaotai Pills not only regulates the central nervous system,but also has a certain protective effect on other organs,reflecting the multi-target and systematic effect of Jiaotai Pills in the treatment of insomnia.