Huang Yun-Fang, Bi Xin-Ning, Zheng Wei, Zhang Ting, Wei Gui-Jie, Zhang Yu-Jie, Wang Qi
School of Chinese Materia Medica, Bejing University of Chinese Medicine Beijing 102488, China.
School of Chinese Materia Medica, Bejing University of Chinese Medicine Beijing 102488, China Beijing Shuanghe Pharmaceutical Co., Ltd. Beijing 100079, China.
Zhongguo Zhong Yao Za Zhi. 2020 May;45(9):2172-2179. doi: 10.19540/j.cnki.cjcmm.20191230.402.
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.
为探讨心肾不交型失眠的发病机制及交泰丸的调节作用，以研究大鼠中枢及外周神经递质的变化。通过腹腔注射对氯苯丙氨酸（PCPA，400mg·kg⁻¹·d⁻¹）诱导心肾不交型失眠大鼠，将造模成功的大鼠灌胃给予交泰丸（3.3g·kg⁻¹·d⁻¹），连续7天。采用超高效液相色谱-串联质谱（UPLC-MS/MS）和主成分分析（PCA）方法测定大鼠血清、尿液、脑、心、肝、肾及肾上腺中9种神经递质。结果显示，失眠大鼠血小板中5-羟色胺（5-HT）和5-羟吲哚乙酸（5-HIAA）的比值显著低于正常组，交泰丸有显著的上调或下调作用。与正常组相比，失眠大鼠血液中变化的神经递质有5-HIAA、肾上腺素（E）、去甲肾上腺素（NE）、多巴胺（DA）、谷氨酸（Glu）和乙酰胆碱（ACH），除ACH外，尿液中7种神经递质的变化更显著，交泰丸有显著的上调或下调作用。与正常组相比，失眠大鼠除高香草酸（HVA）外的8种神经递质均发生变化。交泰丸可调节失眠大鼠各组织中的神经递质，尤其对脑、肝和肾上腺组织作用明显。综上所述，失眠不仅是由脑内神经递质变化引起，还涉及外周组织的一系列变化。这表明失眠是神经递质的系统性失衡。交泰丸不仅调节中枢神经系统，还对其他器官有一定保护作用，体现了交泰丸治疗失眠的多靶点和系统性作用。
