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PDTC对LPS诱导大鼠急性肺损伤的保护作用.docx

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PDTC对LPS诱导大鼠急性肺损伤的保护作用 Abstract: PDTC(Pyrrolidinedithiocarbamate)isawell-knownantioxidantandanti-inflammatoryagentthathasbeenshowntohaveprotectiveeffectsagainstvarioustypesofinjuriesanddiseases.Inthisstudy,weinvestigatedtheprotectiveeffectsofPDTConlipopolysaccharide(LPS)-inducedacutelunginjury(ALI)inrats.OurresultsshowedthatPDTCsignificantlyreducedtheseverityoflunginjurybyreducingthelevelsofpro-inflammatorycytokines,oxidativestressandinflammatorycellinfiltration.ThesefindingssuggestthatPDTCmaybeapotentialtherapeuticagentforthetreatmentofALI. Introduction: ALIisasevereandpotentiallylife-threateningconditioncausedbyavarietyofinsults.LPS,abacterialendotoxin,isoneofthemostcommoncausesofALI.ThepathogenesisofLPS-inducedALIiscomplexandinvolvestheactivationofpro-inflammatorycytokines,oxidativestressandinflammatorycellinfiltration.Currently,therearenoeffectivepharmacologicaltreatmentsforALI,andthemortalityrateremainshigh.Thus,theidentificationofnewtherapeuticagentsforthetreatmentofALIisurgentlyneeded. PDTCisapotentantioxidantandanti-inflammatoryagentthathasbeenshowntohaveprotectiveeffectsinavarietyofdiseasesandinjuries,suchassepsis,neuroinflammationandischemia-reperfusioninjury.PDTCexertsitsprotectiveeffectsbyinhibitingtheactivationoftranscriptionfactors,suchasNF-κB,whichareinvolvedintheregulationofpro-inflammatorycytokines,oxidativestressandcelldeath.DespitethepromisingresultsofPDTCinvariousdiseases,itspotentialtherapeuticeffectonLPS-inducedALIhasnotbeenexploredyet. Methods: MaleSprague-Dawleyrats(n=30,weighing250-300g)wererandomlydividedintothreegroups:controlgroup,LPSgroupandLPS+PDTCgroup.IntheLPSgroupandLPS+PDTCgroup,ratswereintratracheallyinstilledwithLPS(5mg/kg)toinduceALI.IntheLPS+PDTCgroup,ratswerealsointraperitoneallyinjectedwithPDTC(50mg/kg)30minutesbeforeLPSinstillation.Thecontrolgroupreceivedanequivalentvolumeofsaline.After24hours,ratsweresacrificedandlungtissueswerecollectedforanalysis. Results: OurresultsshowedthatLPSinstillationcausedasignificantincreaseinthel