急性电离辐射早期损伤大鼠尿液代谢标志物筛选的分析-screening of urine metabolic markers in rats with acute ionizing radiation-induced early injury.docx

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急性电离辐射早期损伤大鼠尿液代谢标志物筛选的分析-screening of urine metabolic markers in rats with acute ionizing radiation-induced early injury.docx

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急性电离辐射早期损伤大鼠尿液代谢标志物筛选的分析-screening of urine metabolic markers in rats with acute ionizing radiation-induced early injury

英文摘要急性电离辐射早期损伤大鼠尿液标志物筛选的研究SelectionofMetabolicBiomarkersfromRatUrineAppliedintheEarlyStageofAcuteIonizingRadiationDamageAbstractWiththerampancyofaglobalterroristactivitiesincludingnuclearterrorismis,frequencyofnuclearaccidentsintheprocessofpeacefuluseofnuclearenergyandwideapplicationofradioactivesourceinthemedicine,thepotentialriskofradiationdamagefromordinarypeopleincreasessignificantly,andaalarge-scaleradiologicalincidentmayoccuratanytime.Thebiomarkersintheearlystageofacuteionizingradiationfortherapidradiationtriageareimportantfortherapidradiationtriage,rationalusageoflimitedmedicalresourcesandscientifictreatmentstrategy.Inthisresearch,Wistarratsweretheresearchobject,theacuteradiationdamagebiomarkersintheurineareselectedbygaschromatography-massspectrometry(GC-MS)andaminoacidtargetanalysisbasedonliquidchromatography-tandemmassspectrometry(HPLC-MS/MS)techniques.Moreover,themetabolicpathwaysinvolvedintheradiationdamagewereexplored.TheuntargetedmetabolomicmethodbasedontheGC-MSintheurinesamplesfromratswasestablished.Theurinesamplespretreatmentmethodsandtheanalyticalconditionsofgaschromatographyandmassspectrometrywereoptimized.Then,therepeatofsamplepretreatmentmethods,theinter-dayprecisionandintra-dayprecisionwerealsorepresented.Finally,theurinemetaboliteswereidentifiedbyautomatedmassspectraldeconrolutionandidentificationsystem(AMDIS)andretentionindex.ThechangesofmetaboliteslevelsfromurinesampleswereinvestigatedusingtheuntargetedmetabolomicmethodbasedontheGC-MSandaminoacidtargetanalysismethodbasedonliquidchromatography-tandemmassspectrometry(HPLC-MS/MS).Geneticalgorithm(GA)andmultiplestepwiselinearregression(MLSR)werebothusedtoselectedtheradiationdamagecharacteristicdifferencesmetabolites.Fortheconvenienceofclinicalapplication,thebestpanelofpotentialradiationdamagebiomarkerswasscreenedthroughmultiplemeansandthenwasappliedtotheseparationofdifferentdosesgroupsandearlyradiationdamagetriage.急性电离辐射早期损伤大鼠尿液标志物筛选的研究英文摘要Thetopologynetworksamongradiationdamagecharacteristicmetab