重组人血小板源性生长因子增加细胞外信号调节激酶磷酸化促进糖尿病大鼠全层皮肤缺损创面愈合VIP专享VIP免费

RecombinantHumanPlatelet-derivedGrowthFactorEnhancesRepairofCutaneousFull-thicknessExcisionbyIncreasingthePhosphorylationofExtracellularSignal-regulatedKinaseinDiabeticRatCHENGBiao1LIUHongwei1FUXiaobing2SHENGZhiyong2SUNTongzhu2【Abstract】ObjectiveToinvestigatethepossiblesignalingmechanismsbywhichrecombinanthumanplatelet2derivedgrowthfactor(rhPDGF)acceleratedhealingofcutaneouswoundindiabeticrats.MethodsFourfull2thicknessskinwoundswereincisedinthebackof26maleWistardiabeticrats.Thewoundedratsweredividedinto3groups(7or8ratseachgroup).Onegroupwithouttreatmentwasusedasacontrol,andtheother2groupsweretreatedwithrhPDGFatadoseof710Λg�cm2woundorvehicle(DMSO�019%NaCl,vol�vol1∶1)from1to14days.Thewoundhealingwasevaluatedbythemeasurementsofthewoundvolumeandarea.Immunofluorescentandimmunohistochemicalstainingwereusedtoexaminethephosphorylationofextracellularsignal2regulatedkinase1�2(ERK1�2)andtheexpressionofproliferativecellnuclearantigen(PCNA),respectively.ResultsGranulationtissueappearedinthebedofwoundafterinjury.ThenumberofbloodcapillarybudsandfibroblastswasgreaterintherhPDGF2treatedgroupthanthatintheother2groups.Alotofinflammatorycellsinfiltrationandcollagendepositionwereobservedinthewound.Thewound2volumeintherhPDGF2treatedgroupwassmallerthanthatincontrolgroup(P<0.05).ThereepithelializationrateinrhPDGF2treatedgroupwashigherthanthatintheother2groupsat7daysafterinjury(P<0105).TheexpressionofPCNAinreparativecellswashigherinrhPDGF2treatedgroupthanincontrolgrouporvehicle2treatedgroupat3,7daysafterinjury(P<0105).ThephosphorylationofERK1�2wasstrongerinrhPDGF2treatedgroupthanthatincontrolgrouporvehiclegroupat7and14daysafterinjury(P<0105).ConclusionTheseresultssuggestthatrhPDGFaccelerateswoundhealingandimproveshealingqualitybyincreasingthephosphorylationofERK1�2.【Keywords】DiabeticPlatelet2derivedgrowthfactorWoundhealingExtracellularsignal2regulatedkinaseFoundationitems:NationalBasicScienceResearchandDevelopmentGrants(2005CB522603);NationalNaturalScienceFoundationofChina(30170966,30230370);NationalOutstandingYoungResearcherFoundationofChina(39525024);NationalPostdoctoralScienceFoundationofChina(2001.14)BACKGROUNDTissuerepairinvolvesthecoordinatedinteractionofnumerouscelltypesintheprocesses,includinginflammation,matrixdeposition,andremodeling,whichrestorethecontinuityandarchitectureofskin.Themostcommonchronicwoundsincludepressureulcers,diabeticulcers,arterialocclusivediseaseandvenousulcers.Diabetesmellitusisone1DepartmentofPlasticSurgery,GuangzhouGeneralHospitalofGuangzhouMilitaryRegion,GuangzhouGuangdong,510010,P.R.China;2WoundHealingandCellBiologyLaboratory,InstituteforBasicResearch,TraumaCenterofPostgraduateMedicalCollege,GeneralHospitalofPLA,Beijing,100853,P.R.ChinaCorrespondingauthor:FUXiaobing,professor,WoundHealingandCellBiologyLaboratory,InstituteforBasicResearch,TraumaCenterofPostgraduateMedicalCollege,GeneralHospitalofPLA,Beijing,100853,P.R.China,E2mail:fuxb@cgw.net.cnofthemajorcontributorstochronicwoundhealingproblems.Diabeticwoundsrepresentasignificanthealthcareburdenintheworld[1,2].Thepathologicprocessofdiabeticimpairedhealingiscomplex.Althoughitiswellacceptedthatdiabeticwoundshealpoorly,themechanismsunderlyingthisphenomenonarenottotallyunderstood.Ithasbeendemonstratethatdiabeticwoundshaveadeficiencyofgrowthfactors,aprolongedinflammatorystate,andimpairedcellmigrationa...