肠淋巴再灌注加重SMAO休克大鼠炎症反应的机制研究

肠淋巴再灌注加重SMAO休克大鼠炎症反应的机制研究摘要：

目的：本研究旨在探究肠淋巴再灌注加重肠系膜动脉阻断引起的休克大鼠炎症反应的机制。

方法：本研究将40只SD大鼠分为四组：对照组、单纯肠系膜动脉阻断组、单纯肠淋巴再灌注组和肠系膜动脉阻断加肠淋巴再灌注组。通过检测大鼠的炎症反应指标（白细胞计数、肝脾指数、C-反应蛋白、乳酸、肠道黏膜病变程度等）和组织病理学变化，以及病理变化相关指标（P65、IL-1β、TNF-α、MyD88等），来分析肠淋巴再灌注对于肠系膜动脉阻断引起休克大鼠炎症反应的影响及机制。

结果：肠系膜动脉阻断加肠淋巴再灌注组大鼠的炎症反应指标和组织病理学变化明显高于其他组（P<0.05），肠道黏膜病变程度明显增加（P<0.05），而且病理变化相关指标（P65、IL-1β、TNF-α、MyD88等）也有明显的上升趋势（P<0.05）。

结论：肠淋巴再灌注加重肠系膜动脉阻断引起休克大鼠炎症反应，可能与从肠淋巴系统释放的炎症因子与肠道黏膜屏障的破坏有关。

关键词：肠淋巴再灌注，肠系膜动脉阻断，休克大鼠，炎症反应。

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