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Ginkgo Biloba Intervention Study On Serum Lipidomics Of Hyperuricemia

Posted on:2017-12-07Degree:MasterType:Thesis
Country:ChinaCandidate:S L ZhangFull Text:PDF
GTID:2434330482485687Subject:Drug Analysis
Abstract/Summary:PDF Full Text Request
Hyperuricemia is a metabolic disease caused by the disorder of purine metabolism in the body,the relationship between hyperuricemia and lipid metabolism disorders is particularly important,but there is no clear explanation the molecular mechanism now.Ginkgo biloba leaf is a common clinical Chinese medicine,which has the effect of lowering uric acid and lowering blood lipid,but the mechanism of lowering uric acid and the correlation between lowering blood fat and uric acid is not clear.So the intervention mechanism of ginkgo leaf on hyperuricemia has to be further developed.Lipidomics provides a powerful means for prevention,control,diagnosis of lipid metabolism disease,lipid biomarkers,drug target identification and drug development.Therefore,a metabonomic method based on UPLC-Q-TOF/MS and UPC2-Q-TOF/MS were developed to study the lipid metabolic changes in the development of hyperuricemia,the aim of my study is to elucidate inherent mechanism of hyperuricemia and the therapeutic effect of Ginkgo biloba.The main research contents are as follows:1.Study on serum lipidomics in rats with hyperuricemiaA serum metabonomic profiling method based on ultra-performance liquid chromatography/time-of-flight mass spectrometry(UPLC-Q-TOF/MS)and Chromatography-quadrupole-time of flight mass spectrometry(UPC2-Q-TOF/MS)were applied to investigate the metabolic changes in hyperuricemia rats induced by D-fructose,26 potential biomarkers in rat serum were screened out,mainly includes glycerol phospholipids,glycerol lipids and fatty acids.Furthermore,Metabolomics Pathway Analysis(MetaPA)was introduced to deeply analyze unique pathways of hyperuricemia that were primarily involved in Glycerol phospholipid metabolism,linoleic acid metabolism,arachidonic acid metabolism.The result shows that the changes of lipid metabolism during the development of hyperuricemia,and has important significance for the early discovery,early prevention of hyperuricemia.2.Study on serum lipidomics in rats with the intervention of Ginkgo biloba leafUltra-performance liquid chromatography/time-of-flight mass spectrometry(UPLC/TOF-MS)combined with pattern recognition approaches were used to determine differentiating metabolites in serum of control group,model group,benzbromarone group and different doses of EGB,Metabolomics Pathway Analysis(MetaPA)was introduced to deeply analyze clarify the mechanism of Ginkgo biloba leaf in the treatment of hyperuricemia.The result of the research:(1)biochemical examination shows that the serum uric acid and triglyceride of model group were significantly higher than the control group,but after intervention of Ginkgo biloba and benzbromarone,the levels of serum uric acid and triglyceride levels were significantly decreased compared with the model group,which shows that Ginkgo biloba and benzbromarone has similar effect of lowering blood uric acid and lowering blood lipid.(2)Screening of different metabolites:PCA and PLS-DA score plots of model group clustered separately from that of the control,while groups treated with Ginkgo biloba and benzbromarone clustered closely with the control.This result indicates that the hyperuricemia model was successfully constructed,Notably,benzbromarone and Ginkgo biloba exhibited a potential pharmacological effect by regulating multiple perturbed pathways to the normal state.20 potential biomarkers in rat serum were screened out after the intervention of benzbromarone,mainly include glycerol phospholipids and glycerol lipids.12 metabolites were significant in explaining the therapeutic mechanism of Ginkgo biloba extract.(3)Metabolic pathway analysis:Metabolomics Pathway Analysis(MetaPA)was introduced to deeply analyze unique pathways of Ginkgo biloba extract and benzbromarone intervention treatment of hyperuricemia that were primarily involved in Glycerol phospholipid metabolism.The research indicated that Ginkgo biloba and Malone can not only reduce the uric acid,but also improve the lipid disorder,which explained the correlation between uric acid and lipid disorder from the metabolic level,our study has investigated and explained the nature of hyperuricemia and the effect mechanism of EGB by metabolomics method and biochemical assessed values,which shed a new light to the treatment strategy on hyperuricemia and increased more experimental basis for the clinical application of the reduction of uric acid for Malone.In this study,the lipidomics combine chemical indexes and metabolic pathway analysis method to research lipid metabolic changes in the process of hyperuricemia development.We found the biomarkers of hyperuricemia and the establishment of related metabolic pathways,which provided new ideas for early diagnosis,early prevention and early treatment of hyperuricemia.Futhennore,we study the effects of Ginkgo biloba extract intervention on hyperuricemia mechanism and construct the related metabolic pathways of Gingko biloba extract treatment.Not only the result provides new theoretical basis for uric acid lowering mechanism of Ginkgo biloba leaves,also a scientific basis for Ginkgo biloba stem pre-treatment of hyperuricemia.
Keywords/Search Tags:Hyperuricemia, GBE, Lipidomics, UPLC-Q-TOF/MS, UPC~2-Q-TOF/MS
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