植物乳杆菌通过调控胆汁酸代谢并抑制海马体NLRP3蛋白表达缓解铅暴露导致的小鼠学习记忆障碍

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Abstract：ObjectiveToexplorethemechanismofLactobacilusplantarum （L.plantarum）foralleviating learningandmemory impairments caused by lead exposure.Methods Twenty-four C57BL/6Jmice were randomized equallyintocontrol group， lead exposure （100mg/L ） group，and L.plantarum treatment group with daily gavage of L.plantarum （ 109 CFU） for 10 weeks. Learningandmemoryabilitiesof themicewereevaluatedusingMoriswatermazetest，andbloodleadlevelandbileacid levelswere determinedusing inductivelycoupled plasma mass spectrometry （ICP-MS）andliquidchromatography-mass spectrometry （LC-MS），respectively.Hippocampal pathologiesofthemicewereexamined withHEstaining，and immunohistochemistrywasused toobservemorphological changesandmicrogliaactivationinthehippocampus.Serum levelsof TNF- α and IL-1βof the mice were determined with ELISA，and hippocampal expressionlevelsof NLRP3 and TGR5 proteins were detected using Western bloting. Results Compared with those in lead exposure group， the mice receiving L plantarum intervention showed significantlyincreased exploration time，swimming distance，and target platformcrossings withreducedlatencyperiodtofindthehiddenplatformsinMorris watermazetest.L.plantaruminterventionpartiallreversed leadexposureiduceductionofumlevelsofoxolcacidrodeoxholicciddroxursodelic acid，3-thiodeoxycholic acid，and 3-thio ⋅α -methylcholic acid. The treatment also significantly reduced hippocampus pathologies in mice with lead exposure，and reduced their serum levels of IL-1β and TNF- ⋅α and hippocampal NLRP3 protein expresionlevels.ConclusionL.plantarumcanalleviatelearningandmemoryimpairmentscausedbyleadexposureinmice possibly byregulating bileacid metabolismand inhibitinghippocampal expressonof NLRP3 protein.

Keywords：leadexposure;learningandmemory;Lactobacillusplantarum;targetedmetabolomics;NLRP3铅是一种地壳中含量丰富的重金属元素，具有熔点低、耐腐蚀性强、塑性好等特性，被广泛应用于化工、蓄电池制造等领域。（剩余12642字）