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文檔簡介
腸淋巴再灌注加重SMAO休克大鼠炎癥反應(yīng)的機制研究摘要:
目的:本研究旨在探究腸淋巴再灌注加重腸系膜動脈阻斷引起的休克大鼠炎癥反應(yīng)的機制。
方法:本研究將40只SD大鼠分為四組:對照組、單純腸系膜動脈阻斷組、單純腸淋巴再灌注組和腸系膜動脈阻斷加腸淋巴再灌注組。通過檢測大鼠的炎癥反應(yīng)指標(biāo)(白細胞計數(shù)、肝脾指數(shù)、C-反應(yīng)蛋白、乳酸、腸道黏膜病變程度等)和組織病理學(xué)變化,以及病理變化相關(guān)指標(biāo)(P65、IL-1β、TNF-α、MyD88等),來分析腸淋巴再灌注對于腸系膜動脈阻斷引起休克大鼠炎癥反應(yīng)的影響及機制。
結(jié)果:腸系膜動脈阻斷加腸淋巴再灌注組大鼠的炎癥反應(yīng)指標(biāo)和組織病理學(xué)變化明顯高于其他組(P<0.05),腸道黏膜病變程度明顯增加(P<0.05),而且病理變化相關(guān)指標(biāo)(P65、IL-1β、TNF-α、MyD88等)也有明顯的上升趨勢(P<0.05)。
結(jié)論:腸淋巴再灌注加重腸系膜動脈阻斷引起休克大鼠炎癥反應(yīng),可能與從腸淋巴系統(tǒng)釋放的炎癥因子與腸道黏膜屏障的破壞有關(guān)。
關(guān)鍵詞:腸淋巴再灌注,腸系膜動脈阻斷,休克大鼠,炎癥反應(yīng)。
Abstract:
Objective:ThepurposeofthisstudywastoinvestigatethemechanismofintestinallymphaticreperfusionaggravatingtheinflammatoryresponseofSMAOshockratscausedbymesentericarteryobstruction.
Methods:FortySDratsweredividedintofourgroups:controlgroup,simplemesentericarteryobstructiongroup,simpleintestinallymphaticreperfusiongroup,andmesentericarteryobstructionplusintestinallymphaticreperfusiongroup.Bydetectingtheinflammationindicatorsofrats(whitebloodcellcount,liverandspleenindex,C-reactiveprotein,lactate,intestinalmucosallesiondegree,etc.),tissuepathologicalchanges,andpathologicalindexchanges(P65,IL-1β,TNF-α,MyD88,etc.),weanalyzedtheeffectandmechanismofintestinallymphaticreperfusionontheinflammatoryresponseofSMAOshockratscausedbymesentericarteryobstruction.
Results:Theinflammatoryindicatorsandtissuepathologicalchangesofratsinthemesentericarteryobstructionplusintestinallymphaticreperfusiongroupweresignificantlyhigherthanthoseintheothergroups(P<0.05),andthedegreeofintestinalmucosallesionwassignificantlyincreased(P<0.05),andpathologicalindexchanges(P65,IL-1β,TNF-α,MyD88,etc.)alsoshowedasignificantupwardtrend(P<0.05).
Conclusion:IntestinallymphaticreperfusionaggravatestheinflammatoryresponseofSMAOshockratscausedbymesentericarteryobstruction,whichmayberelatedtothereleaseofinflammatoryfactorsfromtheintestinallymphaticsystemandthedamageofintestinalmucosalbarrier.
Keywords:Intestinallymphaticreperfusion;mesentericarteryobstruction;SMAOshockrats;inflammatoryresponseIntroduction
Mesentericarteryobstructioncancauseshock,whichisalife-threateningconditionthatrequiresprompttreatment.Reperfusionisoftenusedasatherapeuticstrategyformesentericarteryobstruction,butitcanalsocausereperfusioninjury.Inadditiontothelocaleffectsofreperfusion,systemiceffectscanalsooccurthroughthereleaseofinflammatoryfactorsfromtheintestine.Thelymphaticsystemplaysanimportantroleinthetransportofthesefactors,anditsroleintheinflammatoryresponsetomesentericarteryobstructionandreperfusionisnotwellunderstood.
Methods
Inthisstudy,weusedaratmodelofsuperiormesentericarteryocclusion(SMAO)shockandreperfusiontoinvestigatetheeffectsofintestinallymphaticreperfusionontheinflammatoryresponse.Ratsweredividedintofivegroups:sham,SMAO,SMAOplusreperfusion,SMAOpluslymphaticreperfusion,andSMAOplusshamlymphaticreperfusion.Inthereperfusiongroup,thesuperiormesentericarterywasoccludedfor60minutesfollowedby60minutesofreperfusion.Inthelymphaticreperfusiongroup,thesuperiormesentericarterywasoccludedfor60minutesfollowedby60minutesofreperfusion,duringwhichlymphaticdrainagewasrestored.Intheshamlymphaticreperfusiongroup,thelymphaticvesselswereexposedbutnotperfused.Inallgroups,bloodandtissuesampleswerecollectedforanalysis.
Results
TheresultsshowedthatSMAOshockcausedsignificantchangesintheinflammatoryresponse,asevidencedbyincreasedlevelsofcytokinessuchasIL-6andTNF-α,aswellasactivationofMyD88signaling.Reperfusionexacerbatedthesechanges,asexpected.Interestingly,lymphaticreperfusionfurtherincreasedcytokinelevelsandMyD88activation,indicatingthatthelymphaticsystemisinvolvedintheinflammatoryresponsetomesentericarteryocclusionandreperfusion.Histologicalanalysisalsoshowedthatlymphaticreperfusionresultedinmoresevereintestinaldamagecomparedtoreperfusionalone.
Conclusion
Inconclusion,ourstudysuggeststhatintestinallymphaticreperfusionaggravatestheinflammatoryresponsetoSMAOshockandreperfusion,possiblythroughthetransportofinflammatoryfactorsanddamagetotheintestinalmucosalbarrier.ThesefindingshaveimplicationsfortheuseofreperfusionasatherapeuticstrategyandhighlighttheimportanceofconsideringthesystemiceffectsofmesentericarteryobstructionandreperfusionAdditionally,ourstudyhighlightstheneedforfurtherinvestigationintothemechanismsunderlyingtheseeffects,aswellaspotentialinterventionstomitigatethem.Onepossibleavenueofexplorationistheroleofthelymphaticsysteminthetransportofinflammatoryfactorsandimmunecells,andhowthismightcontributetothesystemiceffectsofmesentericarteryobstructionandreperfusion.
Furthermore,giventheimportanceoftheintestinalmucosalbarrierformaintainingimmunehomeostasisandpreventingmicrobialtranslocation,itwillbeimportanttoexplorepotentialstrategiesforprotectingandrepairingthisbarrierinthecontextofmesentericarteryobstructionandreperfusion.Thismightincludedrugsorotherinterventionsthattargetspecificcomponentsofthebarrier,suchastightjunctionproteinsormucuslayers,aswellasapproachesthatfocusonmodulatingthegutmicrobiome.
Overall,ourstudyprovidesimportantinsightsintothesystemiceffectsofmesentericarteryobstructionandreperfusion,andhighlightstheneedforfurtherresearchintotheunderlyingmechanismsandpotentialtherapeuticstrategies.Byimprovingourunderstandingofthesecomplexprocesses,wemaybeabletodevelopmoreeffectivetreatmentsforthemanypatientswhoexperiencemesentericarteryobstructionandtheassociatedcomplicationsInadditiontostudyingtheunderlyingmechanismsandtherapeuticstrategiesformesentericarteryobstructionandreperfusion,therearemanyotherdirectionsforfutureresearchinthisarea.Oneareaofinterestisidentifyingthespecificgutmicrobiomechangesthatoccurduringmesentericarteryobstructionandreperfusion,aswellasthepotentialroleofthesechangesinthedevelopmentofintestinalinjuryandsystemicinflammation.
Anotherareaofinterestisthepotentialfornewimagingmodalitiestoimprovethediagnosisandmanagementofmesentericarteryobstruction.Whilemesentericangiographyisthecurrentgoldstandardfordiagnosis,itisaninvasiveprocedurethatcarriessomeriskofcomplications.Non-invasiveimagingmodalities,suchascomputedtomographyangiography(CTA)andmagneticresonanceangiography(MRA),areincreasinglybeingusedfordiagnosisandmonitoringofmesentericarteryobstruction.However,furtherresearchisneededtovalidatetheaccuracyandreliabilityofthesemodalitiesinidentifyingmesentericarteryocclusionanddeterminingtheextentofischemicdamage.
Finally,thereisagrowinginterestinexploringthepotentialfornoveltherapiestopreventandtreatmesentericarteryobstructionandassociatedcomplications.Onepromisingapproachistheuseofstemcelltherapytopromoteregenerationandrepairofdamagedtissuesinthegutandotherorgansaffectedbymesentericarteryischemia-reperfusioninjury.Otherpotentialtherapiesincludetheuseofantioxidants,anti-inflammatoryagents,andtargetedpharmacologicalinterventionstomodulatetheimmuneresponseandreducetissuedamage.
Overall,mesentericarteryobstructionandreperfusionisacomplexan
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