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Analysis Of Cellular Immune Phenotype In Coronary Heart Disease With Qi Deficiency Syndrome And Network Pharmacology Study On Intervention Targets Of Buqi Formula

Posted on:2021-02-02Degree:MasterType:Thesis
Country:ChinaCandidate:Q Y LiFull Text:PDF
GTID:2404330602992904Subject:Integrative Medicine
Abstract/Summary:PDF Full Text Request
Coronary heart disease(CHD)is a chronic inflammatory disease with high mor-bidity and mortality.At present,the etiology and pathogenesis of CHD have not been fully elucidated.In recent years,it has been found that immune-mediated inflammation plays an important role in the pathogenesis of CHD.Lymphocytes are widely distrib-uted in the body as an important part of the immune system,and the role of T lympho-cytes in the pathogenesis of CHD cannot be ignored.Atherosclerosis(AS)is the main cause of CHD.Plaque contains a large number of T lymphocytes,mainly CD4+T cells,which can be divided into multiple cell subgroups based on different phenotypes.Com-pared with acute coronary syndrome(ACS),stable coronary artery disease(SCAD)has the characteristics of slow progress and relatively stable condition.Therefore,clinical attention is not paid enough to its diagnosis and treatment,but its incidence is increasing year by year.Correct understanding of SCAD helps to reduce the rate of misdiagnosis and missed diagnosis in the clinic and improve the diagnosis and treatment.The main symptoms of SCAD are intermittent chest tightness and chest pain.It can appear short-ness of breath,fatigue,palpitations,and syncope with or without angina,which belongs to the category of "thoracic paralysis" in Chinese medicine.Qi deficiency syndrome is one of the main syndromes of chest impediment(Xiongbi).Qi deficiency syndrome is closely related to the level of inflammation in patients with CHD.To our knowledge,there are few studies on immune indicators in patients of qi deficiency syndrome of SCAD.Therefore,in this study,a case-control study was adopted to explore the differ-ences in CD4+T cell subsets in peripheral blood serum of patients with qi deficiency syndrome of SCAD by flow cytometry.The mechanism of action provides a direction for further exploration of the immune-mediated inflammation response and material basis of qi deficiency syndrome of SCADPart 1 Study on the distribution of CD4+T cell subsets in serum of patients with SCAD and qi deficiency syndromeObjective:To observe the distribution of CD4+T cell subsets in peripheral bloodserum of patients with SCAD and qi deficiency syndrome.Methods:In strict accordance with the inclusion and exclusion criteria,a cross-sectional study was used to diagnose CHD through coronary angiography or coronary CTA.The diagnosis of TCM syndromes was confirmed by two experts.There were 30 patients with qi deficiency syndrome in SCAD,and the control group were those who met the standard of healthy subjects and had no qi deficiency syndrome in TCM syn-drome.30 cases were included in control group.Baseline characteristics of all patients were measured,including blood routine,urine routine,stool routine,and blood bio-chemical tests.Flow cytometry was used to compare the percentages of Th1 cells,Th2 cells,Th17 cells,and regulatory T cells(Treg)four CD4+T cell subsets in the periph-eral blood of normal controls and patients with SCAD.Results:? Compared with the control group,the expression of Th1 in the SCAD group increased,and the difference was statistically significant(P<0.05);?Compared with the control group,the expression of Th2 in the SCAD group was sig-nificantly decreased,and the difference was statistically significant(P<0.01);?Compared with the control group,the expressions of Th17 and Treg in the SCAD group were significantly increased,and the difference was statistically significant(P<0.01);?In terms of immune balance,compared with the control group,the Th1/Th2 ratio of the SCAD group increased,with a significant statistical difference(P<0.01);the Treg/Th17 ratio did not decrease significantly(P>0.05).Conclusion:The phenotype of CD4+T cell subsets in peripheral blood serum of patients with SCAD deficiency syndrome is significantly different from that of healthy patients.The levels of Thl and Th17 cells increase,the levels of Th2 cells decrease,and the ratio of Thl/Th2 significantly increases,indicating that SCAD patients with qi deficiency the increase of Thl pro-inflammatory factor level and the decrease of Th2 anti-inflammatory factor level,and there is an immune imbalance with a significantly increased Thl/Th2 ratio.The expression of Treg cells in patients with SCAD qi defi-ciency syndrome was significantly increased,which is inconsistent with most previous studies,which may be related to patients taking qi supplementing Chinese medicine Therefore,further study on the mechanism of Buqi recipe affecting the levels of Treg cells is of great significance for revealing the potential intervention targets of traditional Chinese medicine for treating CHD with Qi deficiency syndrome.Part 2 Network pharmacology study of Treg cell activation induced by ginseng and astragalusObjective:To explore the potential active ingredients and mechanism of activa-tion of Treg cells by ginseng and astragalus based on network pharmacological methods.Methods:The TCMSP platform was used to collect the active ingredients and target information of ginseng and astragalus.The GeneCards and PALM-IST platforms were used to collect the target genes related to Treg activation.Cytoscape 3.6.0 was used to construct the "drug-active ingredient-target" network and network analyzer plug-in for topology analysis,gene interaction analysis in STRING database,Metascape database and RStudio for gene ontology(GO)analysis and KEGG signal pathway enrichment analysis.Results:After searching on the TCMSP platform,a total of 42 active components of ginseng and astragalus with OB>30%and DL>0.18 were obtained,corresponding to 304 target genes.After searching on the GeneCards and PALM-IST platforms,"ac-tivate Treg cells" was used for key words,selecting 779 genes related to human Treg cell activation with No.of articles>5;the two were intersected to obtain 89 target genes for ginseng and astragalus-activated Treg cells and 95 potential active ingredients,of which 95 thirteen major active components with a target gene number of 5 or more;gene enrichment analysis revealed that ginseng and astragalus mainly induce Treg cell activation by regulating biological processes such as cytokines,chemokines,transcrip-tion factors,receptor ligand activities,and enzyme activities.Conclusion:This study has initially elucidated the potential active ingredients and mechanism of activation of Treg cells induced by ginseng and astragalus from the per-spective of network pharmacology,and revealed its multi-component,multi-target,multi-pathway integration and regulation effect characteristics,which is the basis for subsequent development.Experimental research provides clues and evidence.
Keywords/Search Tags:coronary heart disease, qi deficiency syndrome, CD4 + T cells, regulatory T cells, ginseng, astragalus
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