Mast Cells and Gastrointestinal Dysmotility in the Cystic Fibrosis Mouse 英文参考文献.docVIP

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Mast Cells and Gastrointestinal Dysmotility in the Cystic Fibrosis Mouse 英文参考文献.doc

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Mast Cells and Gastrointestinal Dysmotility in the Cystic Fibrosis Mouse 英文参考文献

MastCellsandGastrointestinalDysmotilityintheCystic FibrosisMouse RobertC.DeLisle*,LaurenMeldi,EileenRoach,MaureenFlynn,RacquelSewell AnatomyCellBiology,UniversityofKansasSchoolofMedicine,KansasCity,Kansas,UnitedStatesofAmerica Abstract Background:Cysticfibrosis(CF)hasmanyeffectsonthegastrointestinaltractandacommonprobleminthisdiseaseispoor nutrition.IntheCFmousethereisaninnateimmuneresponsewithalargeinfluxofmastcellsintothemuscularisexternaof thesmallintestineandgastrointestinaldysmotility.Theaimofthisstudywastoevaluatethepotentialroleofmastcellsin gastrointestinaldysmotilityusingtheCFmouse(Cftrtm1UNC,Cftrknockout). Methodology:Wildtype(WT)andCFmiceweretreatedfor3weekswithmastcellstabilizingdrugs(ketotifen,cromolyn, doxantrazole)orweretreatedacutelywithamastcellactivator(compound48/80).Gastrointestinaltransitwasmeasured usinggavageofafluorescenttracer. Results:InCFmicegastricemptyingat20minpost-gavagedidnotdifferfromWT,butwassignificantlylessthaninWTat 90minpost-gavage.GastricemptyingwassignificantlyincreasedinWTmicebydoxantrazole,butnoneofthemastcell stabilizers had any significant effect on gastric emptying in CF mice. Mast cell activation significantly enhanced gastric emptyinginWTmicebutnotinCFmice.SmallintestinaltransitwassignificantlylessinCFmiceascomparedtoWT.Ofthe mastcellstabilizers,onlydoxantrazolesignificantlyaffectedsmallintestinaltransitinWTmiceandnonehadanyeffectinCF mice.MastcellactivationresultedinasmallbutsignificantincreaseinsmallintestinaltransitinCFmicebutnotWTmice. Conclusions: The results indicate that mast cells are not involved in gastrointestinal dysmotility but their activation can stimulatesmallintestinaltransitincysticfibrosis. Citation:DeLisleRC,MeldiL,RoachE,FlynnM,SewellR(2009)MastCellsandGastrointestinalDysmotilityintheCysticFibrosisMouse.PLoSONE4(1):e4283. doi:10.1371/journal.pone.0004283 Editor:StefanBereswill,Charite′-Universita¨tsmedizin Berlin,Germany ReceivedDecember11,2008;AcceptedDecember19,2008;PublishedJanuary27,2009 Copy