alzhelmer病模型小鼠海马代谢物早期变化的9.1磁共振频谱分析word格式论文.docx

AbstractAIM：TostudythemetabolitealterationinhippocampiofAlzheimersmiceby usinginvitro9.4Thighresolutionmagneticresonancespectroscopy,andexplore the possibility of biomarkers at early stage of AD.METHODS：Thirty-sixKunMingmicewererandomlydividedintofiveexperimental groupsandonecontrolgroup.Theexperimentalgroupsweresubcutaneouslyinjected withD-galactose（120mg/d2kg）andsodiumnitrite(NaNO2)(90mg/d2kg)daily.The injections were started at the same day for all of mice. Mice of the five experimentalgroupswereinjectedrespectivelyfor30days,40days,50days,60 daysand70days,whilethecontrolgroupwasinjectedwithsalinefor70days. EachgroupwassubjectedtotheMorriswatermazetest(MWM)afterfinishingthe injection.24hourslaterafterMorriswatermazetest，miceweresacrificedand the hippocampi wereremoved. The right hippocampus was grinded into powder for 1H-MRS examination and the left hippocampus was sliced and stained for histopathologicalexamination.TheconcentrationsofmetabolitesincludingNAA (N-acetylaspartate), Glu (glutamate), mI (myo-inositol) and Cho (choine) were analyzed.RESULTS：MWMtestshowedadecreaseinthespatiallearningandmemoryon70 daycamparedtocontrol(P0.05).Histopathologyconfirmedtheneuronalloss, amyloidplaquesandneurofibrillarytanglesinthehippocampiatthelasttwotime points.ThemeanconcentrationofNAAwas3.04±0.28μmol/g,andGluwas 4.00±0.47μmol/ginthecontrolmice.NAAandGluconcentrationsweredecreased ondays30and40.TheconcentrationsofNAAandGludecreasedby60.2%and67% respectively on day40 compared to control (p0.01). Following day 40,NAA and Gluconcentrationsbothincreased,butstillremainedlowerthanthecontrolgroup onday50.Ondays60and70,theconcentrationsofNAAandGludecreasedagain. ThedecreaseofbothNAA(1.82±0.48μmol/g)andGlu(1.81±0.57μmol/g)becamestatisticallysignificantonday70(P0.05).Incontrast,nodifferencesatanytimewerefoundfortheconcentrationsofmIandChocomparedtothecontrolgroup.CONCLUSION：AlzheimersmicecanbeinducedbyinjectingwithD-galactoseand sodium nitrite. 1H-MRS is a useful tool for observing th