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A Metabonomics Study Of Spontaneous Bacterial Peritonitis

Posted on:2013-03-13Degree:MasterType:Thesis
Country:ChinaCandidate:L L NiuFull Text:PDF
GTID:2234330371983280Subject:Clinical Medicine
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Background: Ascites is the most common complication of cirrhosis, and60%of patients with compensated cirrhosis develop ascites within10yearsduring the course of their disease.Spontaneous bacterial peritonitis(SBP)is avery common bacterial infection in patients with cirrhosis and ascites.Whenfirst described, its mortality exceeded90%but it has been reduced toapproximately20%with early diagnosis and treatment. Since theidentification between SBP and uncomplicated ascites is complex and difficult,many patients miss the best treatment window.Therefore,utilizing newtechnologies to look for new biomarkers of SBP has a wide clinical applicationprospect in reducing the mortality, metabolomics is an emerging discipline.Asan new method, it can carry out systematic research on liverdisease from a metabolic point of view. Metabonomics has been established asan extremely powerful analytical tool and hence found successful applicationsin many research areas including molecular pathology and physiology,drugefficacy and toxicity, discovery of biomarkers related to disease, andenvironmental sciences.Since the important function in the metabolism ofliver,this study,by analyzing the uncomplicated ascites and ascites with SBPpatients ascites metabolite profile,has certain guiding significance in earlydiagnosis and prognosis of SBP.Objective: Our study used a metabolomics research platform to analyzethe different metabolic substances in the ascite of cirrhosis and SBP,aimed tofind potential biomarkers,and finally demonstrated metabolomics can be aneffective method to diagnose SBP.Methods: Our study applied high perform liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) to analyze the ascite sampleof56cirrhosis patients, of which30samples were obtained from patiens withuncomplicated ascites and26SBP. The raw date was converted to NetCDFformat by Markerview.To reflect the differences between uncomplicated ascitesand SBP,a multivariate statistical analysis was performed using SIMCA-Psoftware version12.0(Umetrics AB, Umea,Sweden). Principle componentanalysis (PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) models were constructed with RPLCdata. Protential biomarkerswere selected according to Variable importance Project (VIP) in the value, theloading plot and the Score plot.Results:6biomarkers were found in total. Palmitic amide had a higherlevel in SBP patients,while the rest biomarkers had a higher level inuncomplicated ascites groups than in SBP groups, they are Creatinine,MG(20:5),LysoPC(18:1),LysoPC(18:1),Alpha-CEHC.Palm ceramide and lysophosphatidylcholine (18:0) are more likely to be known as the markers.Conclusion:(1) The study reports a metabolomic methods based on HPLC-MS/MS inthe study of ascites specimen;(2)6biomarkers were found in total. They are Palmitic amide,Creatinine,MG(20:5),LysoPC(18:1),LysoPC(18:1),Alpha-CEHC.Palm ceramide and lysophosphatidylcholine (18:0) are more likely to be known as the markers.
Keywords/Search Tags:Spontaneous bacterial peritonitis, metabolomics, multivariate statisticalanalysis, biomarker
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