Probiotics Prevent Intestinal Barrier Dysfunction in Acute Pancreatitis in Rats via Induction of Ileal Mucosal Glutathione Biosynthesis 英文参考文献.docVIP

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Probiotics Prevent Intestinal Barrier Dysfunction in Acute Pancreatitis in Rats via Induction of Ileal Mucosal Glutathione Biosynthesis 英文参考文献.doc

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Probiotics Prevent Intestinal Barrier Dysfunction in Acute Pancreatitis in Rats via Induction of Ileal Mucosal Glutathione Biosynthesis 英文参考文献

ProbioticsPreventIntestinalBarrierDysfunctioninAcute PancreatitisinRatsviaInductionofIlealMucosal GlutathioneBiosynthesis FemkeLutgendorff1,2,RianM.Nijmeijer2,PerA.Sandstro¨m1,LenaM.Trulsson1,Karl-EricMagnusson3, HarroM.Timmerman2,L.PaulvanMinnen2,GerT.Rijkers2,HeinG.Gooszen2,LouisM.A.Akkermans2, JohanD.So¨derholm1* 1Department of Clinical and Experimental Medicine, Division of Surgery, Linko¨ping University, Linko¨ping, Sweden, 2Gastrointestinal Research Unit, Department of Surgery,UniversityMedicalCenter,Utrecht,theNetherlands,3DepartmentofClinicalandExperimentalMedicine,DivisionofMedicalMicrobiology,Linko¨pingUniversity, Linko¨ping,Sweden Abstract Background:Duringacutepancreatitis(AP),oxidativestresscontributestointestinalbarrierfailure.Westudiedactionsof multispeciesprobioticsonbarrierdysfunctionandoxidativestressinexperimentalAP. Methodology/Principal Findings: Fifty-three male Spraque-Dawley rats were randomly allocated into five groups: 1) controls,non-operated,2)sham-operated,3)AP,4)APandprobioticsand5)APandplacebo.APwasinducedbyintraductal glycodeoxycholateinfusionandintravenouscerulein(6h).Dailyprobioticsorplacebowereadministeredintragastrically, startingfivedayspriortoAP.Afterceruleininfusion,ilealmucosawascollectedformeasurementsofE.coliK12and 51 Cr- EDTA passage in Ussing chambers. Tight junction proteins were investigated by confocal immunofluorescence imaging. Ilealmucosalapoptosis,lipidperoxidation,andglutathionelevelsweredeterminedandglutamate-cysteine-ligaseactivity and expression were quantified. AP-induced barrier dysfunction was characterized by epithelial cell apoptosis and alterationsoftightjunctionproteins(i.e.disruptionofoccludinandclaudin-1andup-regulationofclaudin-2)andcorrelated withlipidperoxidation(r.0.8).Probioticpre-treatmentdiminishedtheAP-inducedincreasein E.colipassage(probiotics 57.4633.5vs.placebo223.7693.7a.u.;P,0.001), 51Cr-EDTAflux(16.7610.1vs.32.1610.0cm/s1026;P,0.005),apoptosis, lipid peroxidation (0