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Study Of HIV/AIDS Damp-heat Syndrome Metabonomics

Posted on:2014-01-31Degree:MasterType:Thesis
Country:ChinaCandidate:X W WuFull Text:PDF
GTID:2254330422965671Subject:TCM clinical basis
Abstract/Summary:PDF Full Text Request
Objective: This study uses transcriptomics approach, with the most commonHIV\/AIDS TCM syndrome damp-heat syndrome patients as the research object,compared with the same area of healthy people. Extraction of total RNA subjects inwhole blood, detected HIV\/AIDS endoretention of damp heat differential gene andMicroRNA. The use of seasonal febrile disease by Sanren decoction method for drugintervention of reduction to absurdity, the quantitative PCR technique was used toconfirm the specificity of the gene and MicroRNA HIV\/AIDS endoretention of dampheat, analysis of damp-heat accumulation type corresponding Chinese medicineintervention to patients with partial anomalous changes to the normal outcome of gene,and in-depth analysis of these outcomes related genes and pathways, inspectiontranscriptome HIV\/AIDS endoretention of damp heat of the substance basis, toexplore the molecular mechanism of HIV\/AIDS in damp-heat accumulationformation, construction of HIV\/AIDS endoretention of damp heat molecular network,provide the basis for the TCM syndrome type HIV\/AIDS objective research andtreatment based on syndrome differentiation. The establishment of syndrome oftranscriptomics technology platform, provide ideas and methods of TCM syndromeessence from the transcriptome level.Methods: he specimens were heat from AIDS in Henan province intrinsic cardpatients and healthy controls with area, Western diagnostic criteria by the nationalMinistry of health in2011edition of "AIDS treatment guidelines" diagnostic criteria.The internal accumulation of damp-heat syndrome of TCM diagnostic criteria by thenational research project "HIV/AIDS common syndrome diagnostic scale". DNA chipschip using CapitalBio Corporation, the use of BRB-ArrayTools (Version4.2) softwareto deal with all kinds of gene chip data, application of single variable sample paired Ttest for differences in gene screening, through down-regulation of gene ontology,function and information channel, the main application of DAVID Tools (http://david.abcc.ncifcrf.gov/) on-line analysis, by analysis of gene interactions, themain application of STRING (http://string.embl.de), analysis and BRB-ArrayTools4.2software with transcription factors and related literature, the clustering analysis bystratification cluster, for each chip signal values to the genes as the center, metriccentered correlation, linkage average linkage, two-way laminated clustering ofsamples and a difference signal.Results:The use of BRB-ArrayTools (Version4.2) software to the HIV/AIDS internalaccumulation of damp-heat syndrome patient group and the healthy control groupgene t analysis, data filtering for Percent of data missing or filtered out exceeds50%,Percent of absent (i.e., Detection, Call=A) data exceeds50%standard filter:HIV/AIDS damp-heat group correlation analysis group and the healthy control card:mRNA-MicroRNA105,73target genes, according to the interaction between thetarget gene, consisting of105nodes,180sides of the relationship graph, HIV/AIDSendoretention of damp heat syndrome group and the healthy control group on therelationship between miRNA and mRNA: the73target genes are mainly involved inthe tissue reaction, proliferation, apoptosis,4genes (FOS, CXCR4, CCL4) inBIOCARTA Pertussis toxin-insensitive CCR5Signaling in Macrophage signalpathway. HIV/AIDS endoretention of damp heat syndrome treatment group patientsafter the expression of25genes involved in signal transduction,16. Mainly involvedin apoptosis, inflammation, immune response, metabolism pathway. Through clusteranalysis, expression profile can display gene after treatment compared with beforetreatment significantly reduced gene, has transformed to the normal trend, showingchanges in outcome after the intervention of the drugs the better genes.Conclusion:1, the integration of mRNA gene expression profile chip and the MicroRNA chiptechnology to establish the HIV\/AIDS endoretention of damp heat related molecularinteraction network, study aids endoretention of damp heat molecular mechanism.2, damp-heat accumulation with soup Sanren intervention, differences in gene therapyand outcome tends to normal control group, suggesting Sanren Decoction syndrome iseffective for the treatment of AIDS endoretention of damp heat.3, analysis of the relationship between damp-heat syndrome group and healthy groupdifferences between MicroRNA and target genes, the73related genes mainly involvedin the regulation of tissue reaction, proliferation, apoptosis,3genes (FOS, CXCR4, CCL4) in BIOCARTA Pertussis toxin-insensitive CCR5Signaling in Macrophagesignal pathway.4, damp-heat accumulation with soup Sanren intervention,25differentially expressedgenes to normal. Involved in signal pathway of16. The main outcome gene withenzyme activity, binding protein, modification, signal transduction, immune responseand so on, are involved in carbohydrate metabolism, lipid metabolism, proteinmetabolism, steroid metabolism, carbohydrate metabolism, fatty acid biosynthesispathway, and is involved in cell apoptosis.This study considers it necessary to study points to the transcriptome, crossover studycarried out4aspects of differences in the genetic information and the change rule,differences in gene screening, table mechanism, epigenetic and transcriptionalregulation of microRNA regulation of specific gene cluster, related proteins,metabolic markers of transcription, protein group and metabolic group comparisonand correlation. It can not only find some gene transcription regulation of intrinsickey card to play in the HIV\/AIDS heat. Signal regulation networks can also be relatedto gene regulation clarified and the syndromes of microRNA and its target gene groupestablished. And the interaction of multiple genes interact with regulatory pathway. Inorder to find specific genes associated with AIDS TCM syndrome susceptibility, thenext step and proteomics, metabolomics and systems biology group associated withthe whole group studies, for the TCM syndromes and made breakthrough progress inresearch.HIV\/AIDS endoretention of damp heat occurrence, development, prognosis of keymolecules in key signaling pathways involved in the process of change in the seriousobstacle of signal transduction pathways and gene regulatory networks, HIV\/AIDSendoretention of damp heat in the pathogenesis may be established in the HIV virusinfection on the basis of a class of complex diseases, immunodeficiency, metabolicdisorder caused by the. The research provides theoretical and experimental basis forthese results, the theory of transcriptome revealed polygenic HIV\/AIDS in differentstages of the disease process rule and its molecular mechanism.
Keywords/Search Tags:AIDS, transcriptomics, TCM syndrome, mRNA, microRNA
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