| "Syndrome" is the basis of disease diagnosis,regularity of prescriptions,and observation curative effect in traditional Chinese medicine(TCM),and "prescription" is an important method to treat diseases."Correspondence between prescription and syndrome" refers to the correspondence between the prescription and the syndrome,which is the main treatment of the prescription and the combination of the prescription accord with the patient’s pathogenesis.Prescription and syndrome are two challenges in TCM."Correspondence between prescription and syndrome" suggests us that if study the "syndrome" or "prescription" solely,that may result in deviating from the internal logic of TCM.Studying the prescription and syndrome in combination would help us improve the efficiency of research and is of great significance in clarifying the nature of the syndrome and mechanism of prescription.Insomnia is a common sleep disorder disease.TCM treatment of insomnia has a long history with remarkable curative effect,which is favored by people.Insomnia is called "bu mei","mu bu ming","bu de wo" in TCM.The etiology and pathogenesis of insomnia are complex,the "heart-kidney imbalance" is the most common type.Jiao-Tai-Wan,which is from "Han Shi Yi Tong" written by Han Mao,consists of Rhizoma Coptidis and Cortex Cinnamon(10:1).In this prescription,Rhizoma Coptidis,which is bitter and cold,could clear away exuberant heart-fire;Cortex Cinnamon,which is pungent and hot,could promote the yang and fire.The combination of the two drugs can be used to coordinate heart and kidney,which obtained good results clinically in treating insomnia caused by"heart-kidney imbalance".At present,the study of insomnia caused by "heart-kidney imbalance" mainly focuses on basic theory of,and specific indicators of etiology and pathogenesis is still lacking.The animal model is caused by injecting para-chlorophenylalanine(PCPA)intraperitoneally.PCPA could suppress the synthesis of 5-HT in the brain,which results in the disappearance of the circadian rhythm and the dysfunction of HPA axis.The research on pharmacodynamics of Jiao-Tai-Wan covered all aspects of neuro-endocrine-immune(NEI).In neurological aspect,Jiao-Tai-Wan could regulate disorder of neurotransmitter in brain of PCPA insomniac rats.In endocrine aspect,Jiao-Tai-Wan could regulate hormone in PCPA insomniac rats.In immune aspect,Jiao-Tai-Wan could regulate cytokines to normal level in serum of PCPA insomniac rats.After summarizing former research,we found that those indicators in the brain or serum changed in insomniac,and Jiao-Tai-Wan had regulatory effect.But those research which usually stayed on brain or serum aspect did not reflect the essence of "heart-kidney imbalance"and "coordination between the heart and kidney" and did not reflect holistic view of TCM.The characteristics of syndrome were described by single indicator.There is similarity in theory of "heart-kidney imbalance" and the hypothalamic-pituitary-adrenal axis.Modern medicine also suggests that the excitement and hyperactivity of the HPA axis is an important cause of insomnia.The normal physiological function of HPA axis plays an important role in the homeostasis of the internal environment.The HPA axis is the hub of NEI network.As the participants of NEI network,amino acids neurotransmitters and cytokines are closely related to HPA axis and participate in feedback and negative feedback adjustment of HPA axis,which may be an important mechanism for HPA axis affecting insomnia.Amino acids neurotransmitters and cytokines not only exist in brain,but also exist in other tissues of organism.The relationship between pathological changes of heart,kidney and other tissues involved insomnia caused by heart-kidney imbalance and the disposition of amino acids neurotransmitters and cytokines is unknown.The regulatory effect of Jiao-Tai-Wan is not clear.Membrane protein is the essential protein of normal development and physiology,and plays an important role in diseases such as tumor and nervous system.In known drug targets,about 70%are membrane proteins,and the study of membrane protein would help to understand the disease and find therapeutic targets.What changes in membrane proteome in state of insomnia caused by "heart-kidney imbalance" and the effects of Jiao-Tai-Wan remain to be clarified.In recent years,more and more clinical practice found that Jiao-Tai-Wan not only get good results in treating insomnia,but also can be used for treating depression,climacteric syndrome,diabetes mellitus,skin disease and oral ulcer.The treatment of diabetes mellitus and depression catches people’s attention.Based on the above issues,this research investigated the level of amino acids neurotransmitters and cytokines in different tissues of "heart-kidney imbalance" insomnia rats and regulatory effect of Jiao-Tai-Wan;this research analyzed the membrane proteome in the brain and liver of "heart-kidney imbalance" insomnia rats and regulatory effect of Jiao-Tai-Wan;this research explored the targets of Jiao-Tai-Wan in treating diabetes mellitus,depressive disorder and insomnia and mechanism of treating different diseases with same method.1 Distribution of amino acid neurotransmitters(GABA and Glu)in tissues related HPA axis under the condition of insomnia caused by "heart-kidney imbalance" and regulatory effect of Jiao-Tai-Wan.This part established determination method of amino acid neurotransmitters in rat tissues and plasma with indicator of GABA and Glu and internal standard of 2-pyridylacetic acid.The results showed that Glu levels increased in brain and plasma of model rats while decreased in heart,liver,lung and kidney,which indicated insomnia caused by heart-kidney imbalance is related to amino acid neurotransmitter disorder not only in the brain,but also in tissues related HPA axis.After treatment with Jiao-Tai-Wan,amino acid neurotransmitters in these tissues had a tendency to return to normal.It is speculated that Jiao-Tai-Wan coordinated heart and kidney by regulating levels of amino acid neurotransmitters in tissues.2 Distribution of cytokines(TNF-α and IL-1β)in tissues related HPA axis under the condition of insomnia caused by "heart-kidney imbalance" and regulatory effect of Jiao-Tai-Wan.This part investigated the pathologic changes of insomnia caused by heart-kidney imbalance and the regulatory effect of Jiao-Tai-Wan from cytokine aspect.In the model group,the levels of TNF-α and IL-1β decreased in the heart,liver,kidney and brain,which suggested that insomnia caused by "heart-kidney imbalance" is involved in the disorder of cytokines.That the balance of cytokines was disrupted would have an effect on immune regulation.After treatment with Jiao-Tai-Wan,the levels of TNF-α and IL-1β were up-regulated,indicating that they were used to treat insomnia by regulating the levels of these cytokines.3 The changes of membrane proteome in rat brain and liver under the condition of insomnia caused by "heart-kidney imbalance" and regulatory effect of Jiao-Tai-Wan.At present,the point of view is accepted that insomnia is related to the brain.TCM held that catharsis function of liver has close relation with emotional activity.coordination between the heart and kidney depends on catharsis function of liver.In this chapter,the membrane proteins of brain and liver were analyzed by iTRAQ quantitative proteomics technology.Compared with the normal group,157 and 150 differentially expressed membrane proteins(DEMPs)were identified in the brain and liver of the insomniac group respectively.DEMPs in the brain enriched in 297 biological process such as ion transport and enriched in 22 KEGG pathway such as cholinergic synapse.DEMPs in the liver enriched in 207 biological process such as small molecule metabolic process and enriched in 16 KEGG pathway such as Parkinson’s disease.These results suggested that the membrane proteins associated with various biological process and pathway in the brain and liver changed remarkably.After treatment with Jiao-Tai-Wan,51 and 39 the DEMPs in the brain and liver was normalized involved in high affinity choline transporter 1,COX,adenylate cyclase,UGT and so on.These membrane proteins have important biological functions.Jiao-Tai-Wan normalized proteins in the brain enriched in 100 biological process such as central nervous system development and enriched in 3 KEGG pathway such as Parkinson’s disease.Jiao-Tai-Wan normalized proteins in the liver enriched in 30 biological process such as cellular respiration and enriched in 7 KEGG pathway such as Parkinson’s disease.Jiao-Tai-Wan was used to treat insomnia caused by "heart-kidney imbalance" by regulating these proteins and pathways.4 Network pharmacological mechanism of Jiao-Tai-Wan in treating diabetes mellitus,depressive disorder,insomnia with same methodThis part discussed mechanism of Jiao-Tai-Wan in treating diabetes mellitus,depressive disorder and insomnia with same method at a molecular level using network pharmacology technology.Results manifested that 20 compounds in Jiao-Tai-Wan could act on 92 targets to exert the therapeutic action for three diseases.There are common targets and individual targets for treating diabetes mellitus,depressive disorder and insomnia.The targets of Jiao-Tai-Wan in treating diabetes mellitus mainly enriched in anti-apoptosis biological process and toll-like receptor signaling pathway.The targets of Jiao-Tai-Wan in treating depressive disorder mainly enriched in signal transduction biological process and neuroactive ligand-receptor interaction pathway.The targets of Jiao-Tai-Wan in treating insomnia mainly enriched in serotonin receptor,phospholipase C activating pathway biological process and neuroactive ligand-receptor interaction pathway.Jiao-Tai-Wan showed the characteristics of multi-component,multi-target and multi-pathway.This study can be used as reference for the mechanism of "treating different diseases with same method" of Jiao Tai Wan.In summary,this study investigated the essence of insomnia caused by "heart-kidney imbalance" from the aspect of distribution of amino acid neurotransmitters and cytokines and membrane proteins in the brain and liver and investigated the mechanism of Jiao-Tai-Wan coordinating heart and kidney from above aspects.In addition,the mechanism of "treating different diseases with same method" of Jiao-Tai-Wan was discussed preliminarily using network pharmacology technology.Jiao-Tai-Wan and insomnia caused by "heart-kidney imbalance" were studied systematically with the concept of“correspondence between prescription and syndrome",which provided the basis for the molecular level. |
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