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Evaluation Of Two Animal Models Of Hyperuricemia Based On Lipid Metabolomics

Posted on:2019-03-24Degree:MasterType:Thesis
Country:ChinaCandidate:M Y LiuFull Text:PDF
GTID:2354330545996102Subject:Drug Analysis
Abstract/Summary:PDF Full Text Request
Hyperuricemia is a metabolic disease in which uric acid is increased due to disorders of purine metabolism and/or uric acid excretion in the body.With the continuous improvement of living standards,the incidence of hyperuricemia increases year by year.If the asymptomatic hyperuricemia is ignored,it will cause pain due to inflammation,and even produce tophi,affecting action and life.Hyperuricemia is often associated with coronary heart disease,hypertension,diabetes,obesity,and other diseases.Hyperuricemia is closely associated with disorders of lipid metabolism in the study,explaining hyperuricemia from the perspective of lipid metabolism.The pathogenesis is partic?larly important.Due to the complexity of clinical samples,it is difficult to find patients with simple diseases.Therefore,using animal experiments to explore the disease is particularly important.Through literature review and other external factors,this article selected rodents,fructose,and oxonate potassium as contrast agents for hyperuricemia.Lipidomics is an important branch of metabolomics and specializes in the study of the characteristics of all lipid molecules in organisms.Lipid metabolism has made a breakthrough in the diagnosis of diseases,the identification of lipid biomarkers,and the development of lipid disorder drugs.ultra-high performance liquid chromatography-mass spectrometry(UPLC-Q-TOF/MS)is currently the most widely used metabolomics technology.The combination of the two technologies not only improves the separation ability,but also shortens the analysis time.You can get lower detection limits.Therefore,this study used UPLC-Q-TOF/MS technique lipid metabolomics method,combined with physiological and biochemical indicators and tissue sections,to f?lly characterize the lipid metabolism changes of hyperuricemia,and to explain high uric acid from the perspective of lipid metabolism.The occurrence and development of hyperlipidemia.By comparison,animal models adapted to the development of clinical hyperuricemia were selected.The main research content is as follows:1.Lipidomics study on rat hyperuricemia induced by potassium oxonateUPLC-Q-TOF/MS based lipid metabolomics technique combined with multivariate statistical analysis were used to study the differences in lipid metabolism in hyperuricemia model rats induced by potassium oxonate,and a total of 13 were found by data combination and online database search.Biomarkers of known structures were 10 in positive ion mode and 3 in negative ion mode.These included three phosphatidylcholines,five hemolytic acylcholine,three phosphatidylethanolamines,one hemolytic phosphatidylethanolamine,and one triglyceride.MetPA database analysis of metabolic pathways,found that potassium oxonate led to high uric acid in rats mainly glycerol phospholipid metabolism and glycosylphosphatidylinositol anchor biosynthesis and other two metabolic pathway disorders.2.Lipidomics study on rat hyperuricemia induced by FructoseA multivariate statistical analysis method was used to analyze lipid peroxidation serum-UPLC-Q-TOF/MS data of rats induced by fructose.After identification,a total of 18 important potential biomarkers for serum hyperuricemia were obtained,and positive ion mode 17 One,under negative ion mode.There were 10 phosphatidylcholines,4 hemolytic acylcholine,1 hemolytic cephalin,2 sphingolipids,and 1 triglyceride.Metabolic pathways were analyzed in the MetPA database and it was found that fructose leads to rats.High uric acid is mainly related to the disorder of three metabolic pathways such as metabolism of glycerophospholipids,metabolism of peanut tetradiacid,and metabolism of linoleic acid.By comparing the biochemical markers detected in the two animal models with the analysis of abnormal lipids and metabolic pathways,it was found that the developmental mechanism of fructose-induced hyperuricemia rats is closer to that of clinical samples.To provide scientific and reliable models for follow-up studies,and provide new ideas and methods for the prevention and treatment of hyperuricemia.
Keywords/Search Tags:Hyperuricemia, Lipidomics, UPLS-Q-TOF/MS, Fructose, Potassium oxonate
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