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Plasma Phospholipid Metabolic Profiling And Biomarkers Of Type2Diabetes Mellitus Based On UPLC/Q-TOF MS

Posted on:2013-04-23Degree:MasterType:Thesis
Country:ChinaCandidate:Q L TianFull Text:PDF
GTID:2254330422954679Subject:Drug Analysis
Abstract/Summary:PDF Full Text Request
This paper build a qualitative analysis methods of plasma phospholipid based on theUPLC/Q-TOF MS technology.Also,I conducted a preliminary study on phospholipidmetabolic disorder of T2DM.Through finding the relevant pathological andpharmacological biomarkers for type2diabetes mellitus to provide a new effective waywith drug screening.UPLC/Q-TOF MS has high sensitivity and the high resolution, which is very usefulfor the analysis of the composition of similar complex phospholipids in plasma, thisexperiment set up a stable reverse phase chromatographic separation and analysis methodsof phospholipids in plasma; In normal rats that is four categories of phospholipid,26in total,phosphatidylinositol, phosphatidylcholine, lysophosphatidylcholine and sphingomyelin,respectively. At the same time it also laid a good foundation for the follow-up identificationof biological markers structure.This experiment used high sugar and fat diet and STZ induction method to set up theexperimental type2diabetes model in rats, and employ Glimepiride to intervention themodel, inspected the rats’ plasma phospholipid metabolic differences in differentphysiological pathologic state.In this article, the biomark, mixomics and PLS package of R language used to blankcontrol, model group and the treatment group plasma samples with chemometrics analysis,mainly adopts the unsupervision pattern recognition method (PCA, IPCA, SPCA) andsupervision pattern recognition method (PLS-DA, PCL-DA) method to each sample classification, and through the studentt, Shrinke, PCL-DA, VIP and PLS-DA five methodssearch for potential biomarkers, after processing analysis with Lipidmaps database to findout the total9very important phospholipids biomarkers,8of those are type2diabetespathological markers, has five is which Glimepiride intervention type2diabetes of thepharmacological markers, overlapping four phospholipid is both pathological markers andpharmacological markers.According to these markers tries to reveal the correlation of phospholipids and T2DMmetabolism and Glimepiride’s effects on type2diabetic rats plasma phospholipidsmetabolic, which is benefit to research the mechanism of type2diabetes, screening leadingcompounds,it provide an ideas and methods.
Keywords/Search Tags:Phospholipid, Biomarker, UPLC/Q-TOF MS, Type2Diabetes Mellitus, Chemometrics
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