Humansmallintestineiscapableofrestoringbarrierfunctionaftershortischemicperiods
摘要: AIMToassessintestinalbarrierfunctionduringhumanintestinalischemiaandreperfusion(IR).METHODSInahumanexperimentalmodel,6cmofjejunumwasselectivelyexposedto30minofischemia(I)followedby30and120minofreperfusion(R).Ashamprocedurewasalsoperformed.Bloodandtissuewassampledatall-timepoints.Functionalbarrierfunctionwasassessedusingdual-sugarabsorptiontestswithlactulose(L)andrhamnose(R).Plasmaconcentrationsofcitrulline,anaminoaciddescribedasmarkerforenterocytefunctionweremeasuredasmarkerofmetabolicenterocytesrestoration.Damagetotheepithelialliningwasassessedbyimmunohistochemistryfortightjunctions(TJs),byplasmamarkerforenterocytesdamage(I-FABP)andanalyzedbyelectronmicroscopy(EM)usinglanthanumnitrateasanelectrondensemarker.RESULTSPlasmaL/Rratiosweresignificantlyincreasedafter30minofischemia(30I)followedby30minofreperfusion(30R)comparedtocontrol(0.75±0.10vs0.20±0.09,P<0.05).At120minofreperfusion(120R),ratiosnormalized(0.17±0.06)andwerenotsignificantlydifferentfromcontrol.PlasmalevelsofI-FABPcorrelatedwithplasmaL/Rratiosmeasuredatthesametimepoints(correlation:0.467,P<0.01).TJsstainingshowsdistortionofstainingat30I.AnintactliningofTJswasagainobservedat30I120R.ElectronmicroscopyanalysisrevealeddisruptedTJsafter30Iwithparacellularleakageoflanthanumnitrate,whichrestoredafter30I120R.Furthermore,citrullineconcentrationscloselyparalleledthehistologicalperturbationsduringintestinalIR.CONCLUSIONThisstudydirectlycorrelateshistologicaldatawithintestinalpermeabilitytests,revealingthatthehumanguthastheabilityoftowithstandshortepisodesofischemia,withmorphologicalandfunctionalrecoveryoftheintestinalbarrierwithin120minofreperfusion. ...
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