map4在炎症导致肺微血管通透性增高中的作用及机制的研究

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1、万方数据第三军医大学硕士学位论文APODDABBSAdammoIlimnpersulf．ateopticaldensitydi锄inobenzidinbovineserumalbuminday3过硫酸铵分光光密度二氨基联苯胺牛血清白蛋白天万方数据第三军医大学硕士学位论文TheroleandmechanismsOfMAP4ininnammation—inducedlungmicrovascularhyperpermeabili钾一lndUCenIUngmlCr0VaSCUlarnVDerDermeab¨ltVAbstractBackgrOundSeVerebums1e

2、adtolocalorsystematicactivationofinfl猢ationa11dtheaccompanyingproductionofmanyinfl猢atorymediators，whichcandirectlyorindirectlycaused撇ageofendothelialcellsaJldhype印emeability．LungasabridgetotheenViromnent，itiseasilya髓ctedbymaI】yfactors，whichleadtoincreasedluIlgmicroVascularpe彻eabilityan

3、dacutelunginjury(ALI)．However，therearestillnoea色ctiVewaystodecreasehyperpe吼eability，andtheunderlyingregulatedmechanismsofinnammation—inducedlungmicrovascularhype叩eHneabjlitystilluncle趴Recemly，increasingdatahaVesuggestedthatmicrotubule(MT)isessentialfor也eimegri哆ofendotheIialbarrier，a11d

4、medynamicsofmicmtubulehasassociatedwithmaJlyf如tors，suchasGTP，temperature，dmgsandmicrotubuleassociatedproteins(MAPs)．SomedataindicatedthatMTdisassemblyleadtoinjuryofceUmorph0109yandcell-ceUjunctionalstructures，whichcanbepreVentedbyapplicationofmicrotubulestabiIizer．HoweVer，thedetailedre

5、gulatedmechanismsofmicrotubuleininnammation—inducedendothelialbarrierdysfunctionstiUunknown．Asawell-knowntubulinassociatedprotein，microtubule-aSsociatedprotein4(MAP4)hasplaya11imponantr01einthemaintallenceofstructuresaJlddynamicsofmicrotubule．Onceitisphosphorylated，MAP4dissociatesfromm

6、icrotubule，resultinginMTinStabili何WepreViouslyconfi腿edthatp38／MAPKpatllwayactivationleadtoMAP4phosphorylation、Ⅳithmicrotubuledisassemblyincaridomyocytesduringhypoxia；andp38／MAPKisanimportantsignalpathwayrequiredformicrofil锄entrea仃aJlgementthatprecedesendothelialba玎ierdysfunction．HoweVe

7、r，theinvolVementandtheunderlyingregulatedmechanismsofMAP4inmediatinginn锄mation—inducedendothelialbarrierdysmnctioninALIremainsummown-Thus，wewouldflrstdeteminethatwhetherMAP4(S696，S787，S768)4万方数据第三军医大学硕士学位论文phosphorylationincreaSedininnammation．ThenwewouldconstructaMAP4(Ala)mutaIlt，wh