The Biological Basis Of The Relationship Between The Liver Depression And Heat Dissipation Syndrome And The Optimized Prescription For Qinggan Jieyu

Syndrome is a unique disease cognition view of traditional Chinese medicine,which is the basis of syndrome differentiation and treatment.The biological research of syndrome has always been a hot field of modern Chinese medicine research.Liver depression and heat syndrome is a complex syndrome type,which is caused by liver depression and heat for a long time.It is one of the common clinical complex syndrome types.Relevant research shows that liver depression and heat syndrome involves multiple system pathophysiological changes,but its internal biological basis is not clear.Therefore,based on 155 clinical cases,taking the patients with liver depression and heat syndrome as the research object,Optimizing Qinggan Jieyu Decoction as the intervention method,applying metabonomics and neuro-endocirine-immune(NEI)network,this study analyzed the serum biomarkers of migraine,non organic insomnia and premenstrual syndrome,and discussed the biological markers of the patients with liver depression and heat syndrome The biological markers of syndrome and the potential mechanism of Optimizing Qinggan Jieyu Decoction in the treatment of liver depression and heat syndrome.Objective:To study the changes of serum metabolites and NEI network indexes in the liver depression and heat syndrome,and to evaluate the clinical effect and potential mechanism of Optimizing Qinggan Jieyu Decoction the changes of bioinformatics,serum metabolites and NEI network after the intervention of Optimizing Qinggan Jieyu Decoction in the liver depression and heat syndrome transformation,and to analyze the biological basis of serum associated with the optimization of Optimizing Qinggan Jieyu Decoction and the liver depression and heat syndrome.Method:1.Network pharmacology researchTcmsp(Pharmacology database and analysis platform of traditional Chinese medicine system)was used to collect the main components and potential drug targets of Optimizing Qinggan Jieyu Decoction.The network of potential drug targets of Optimizing Qinggan Jieyu Decoction was visualized with the software of Cytoscape.The target genes corresponding to migraine were obtained in the drug databases OMIM and genecards,and the targets were matched to obtain the active components of Optimizing Qinggan Jieyu Decoction Potential targets for migraine treatment.The protein-protein interaction network is obtained by using string database,and the information is imported into the software of Cytoscape to draw the protein-protein interaction network,The gene ontology(GO)analysis and KEGG pathway enrichment analysis of the target gene of disease drug intersection were carried out with the aid of David online tool.2.MetabonomicsThe serum differential metabolism biomarkers of 45 cases of migraine,non organic insomnia and premenstrual syndrome,45 cases of non liver depression and heat syndrome and 20 cases of healthy people were detected;45 cases of liver depression and heat syndrome were treated with Optimizing Qinggan Jieyu Decoction,and the effect of Optimizing Qinggan Jieyu Decoction on the serum metabolism biomarkers of liver depression and heat syndrome was studied.The data of LC-MS were preprocessed by tracefounder software,and the variables(RT MZ,retention time mass load ratio),molecular weight(compmw),observation quantity(sample)and peak intensity were obtained.The edited data matrix was imported into metaboanalyst4.0 software for principal component analysis(PCA),and metpa software was used to find metabolic pathways related to markers.3.Research on NEI networkThe contents of 5-HT,β-EP,GnRH,ACTH,COR,IL-1β,IL-2,IL-6,TNF-α,INF-y in serum of 45 patients with liver depression and heat syndrome,45 patients with non liver depression and heat syndrome and 20 healthy people were measured.The Optimizing Qinggan Jieyu Decoction was used to treat 90 patients with liver depression and heat syndrome,and its effect on the serum NEI network of 45 patients with liver depression and heat syndrome was studied.Result:1.Research results of network pharmacologyThe information of 6 single drugs,82 ingredients and 4883 targets of Optimizing Qinggan Jieyu Decoction and imported into the software of Cytoscape to build the disease component target network.Then,the merge function of Cytoscape was used to merge the network,remove the irrelevant targets and identify the diseases,ingredients and common targets.The disease component common target network was obtained,involving 141 nodes and 392 edges.After constructing PPI network of drug disease and hiding irrelevant targets,a core target network with 90 nodes and 831 edges of Optimizing Qinggan Jieyu Decoction and three diseases of migraine,non organic insomnia and premenstrual syndrome was obtained.The results of go analysis showed that 100 functional enrichments were obtained,and the biological functions of the target genes of Optimizing Qinggan Jieyu Decoction and migraine,non organic insomnia and non organic insomnia were optimized,including proliferation,nuclear receptor activity,hormone regulation,etc.KEGG results showed that it was mainly involved in the enrichment of 97 key signaling pathways,including hepatitis B(hsa05161),fluid shear stress and atherosclerosis(hsa05418),prostate cancer(hsa05215),apoptosis(hsa04210),tumor necrosis factor signaling pathway(hsa04668),prolactin signaling pathway(hsa04917),p53 signaling pathway(hsa04115))and variety of apoptosis(hsa04215).2.The results of serum metabonomics analysis of liver depression and heat syndrome(1)There are 30 potential serum biomarkers for identification of liver depression and heat syndrome,among which the up regulated ones are aldehydes lysine,4-hydroxyproline,histamine,deoxyribose,3-hydroxy-3-methyl-2-oxbutyric acid,dehydroepiandrosterone,N-(3-oxhexyl)homoserine lactone,succinic acid,creatinine,oligosaccharide,pyruvate,uric acid,uracil,etc.Down regulated were lactate,16 dihydrosphingosine,valine,plant sphingosine,etc.The related metabolic pathways are phenylalanine metabolism,pyruvate metabolism,histidine metabolism,sphingolipid metabolism,glycerol phospholipid metabolism,arginine biosynthesis,glycolysis/gluconeogenesis.(2)The Optimizing Qinggan Jieyu Decoction can recover the biomarkers such as lactate,aldehydelysine,creatinine,hexadecyldihydrosphingosine,histamine and plant sphingosine,and make them tend to the level of healthy people.The metabolic pathway is phenylalanine metabolism,histidine metabolism and glycerophosphingolipid metabolism.3.The change of NEI index and the effect of Optimizing Qinggan Jieyu Decoction(1)Analysis of the therapeutic effect of Optimizing Qinggan Jieyu Decoction on the liver depression and heat syndrome transformation:Optimizing Qinggan Jieyu Decoction has significant therapeutic effect on migraine,non organic insomnia and premenstrual syndrome,which can significantly reduce the Diagnosis and Evaluation Scale score of the liver depression and heat syndrome transformation,and improve the life quality of patients from various dimensions.(2)Changes of NEI related indexes in patients with liver depression and heat syndrome:compared with healthy people,the serum levels of IL-6,IL-1β,TNF-α and 5-HT in patients with liver depression and heat syndrome were all increased.After the treatment of Optimizing Qinggan Jieyu Decoction,the serum level of 5-HT was restored to the level of healthy people,indicating that Optimizing Qinggan Jieyu Decoction may achieve the therapeutic effect by reducing 5-HT.Conclusion:(1)Through the analysis and observation of the target pathway network,combined with the results of GO analysis and KEGG analysis,we speculated that the potential mechanism of Optimizing Qinggan Jieyu Decoction in the treatment of migraine,non organic insomnia and premenstrual syndrome may be related to its participation in the biological processes such as inflammation and oxidation reaction,and the activation of TNF signal pathway may be one of the important links.(2)Through the analysis,it is concluded that the patients with liver depression and heat syndrome mainly have changes in glucose metabolism,lipid metabolism,amino acid metabolism and other aspects compared with healthy people and non liver depression and heat syndrome patients.30 potential biomarkers are screened out,and 7 metabolic pathways are determined through metpa platform,namely alanine metabolism,pyruvate metabolism,histidine metabolism,sphingolipid metabolism,glycerophosphingolipid metabolism Metabolism,arginine synthesis,glycolysis/gluconeogenesis.At the same time,it was found that the mechanism of Optimizing Qinggan Jieyu Decoction in the treatment of liver depression and heat syndrome might involve the intervention of histidine metabolism,glycolysis,lipid metabolism,etc.,and the regulation of metabolic disorders in vivo,so as to play a role in the treatment of liver depression and heat syndrome.(3)The NEI network of patients with liver depression and heat syndrome has abnormal changes,which is manifested by 5-HT metabolic disorder and the increase of immune factors in peripheral blood.There is a certain correlation between the increase of 5-HT and the increase of immune function.Optimizing Qinggan Jieyu Decoction may improve the syndrome of liver depression and heat by regulating the content of 5-HT.(4)Optimizing Qinggan Jieyu Decoction can obviously improve the related symptoms,reduce the frequency of migraine attack,improve the sleep quality,reduce the body E2,improve the quality of life,and show its overall regulatory effect on the syndrome.(5)In this study,the internal mechanism of simultaneous treatment of different diseases and the research mode of syndrome differentiation of new TCM drugs were discussed,which laid a foundation for the later research of liver depression and heat syndrome.