2017.10.23科室讲课 何国栋

RemoteLimbIschaemicPostconditioningProtects

AgainstMyocardialIschaemia/ReperfusionInjury

inMice:ActivationofJAK/STAT3-MediatedNrf2AntioxidantSignallingCellPhysiolBiochemIF：5.104

2017Oct5BackgroudTheJAK-STATsignalingpathwaytransmitsinformationfromextracellularchemicalsignalstothenucleusresultinginDNAtranscriptionandexpressionofgenesinvolvedinimmunity,proliferation,differentiation,apoptosisandoncogenesis.JAKsareessentialmediatorsofthecellularsignalingbycytokinereceptors(IL-2~7,GM-CSF,GH,EGF,PDGF,IFN.FourmembersoftheJAKfamily:JAK1,JAK2,JAK3andTYK2.STAT:SignaltransducersandactivatorsoftranscriptionsevenSTATproteinshavebeenidentifiedinmammaliancells.

Nrf2（nuclear

factor

erythroid

2-related

factor):Nrf2isamasterredoxregulatoroftheantioxidantdefencesystem,includingHO-1,quinoneoxidoreductase-1(NQO1),andSOD.

Nrf2-antioxidantsignallingplaysasignificantroleinprotectingcellsagainstoxidativestress.Underthebasalcondition,Nrf2isretainedinthecytoplasmbyKeap1-CUL3ubiquitinE3ligasecomplex,whichfunctionsasaninhibitorandmediatesthedegradationofNrf2.WhenintracellularROSlevelincreases,theoxidativestresstriggersthedissociationofKeap1-Nrf2complex,allowingNrf2translocatetothenucleuswhereitsubsequentlybindstotheantioxidantresponseelements.Fig.1.Experimentalgroupsandprotocol.Table1.Hemodynamicparameters.Allvaluesareexpressedasmean±SD.n=5forpergroup.Heartrate(HR)andmeanarterialpressure(MAP)weremeasuredatbaselineandduringischemia/reperfusion.**P<0.01VStheircorrespondingBaseline;#P<0.05VStheircorrespondingIRgroups;&

P<0.05VStheircorrespondingRIPostCgroupsFig.2.**P<0.01comparedwithIRgroup;##P<0.01comparedwithRIPostCgroup.Fig.3.**P<0.01comparedwithIRgroup;##P<0.01comparedwithRIPostCgroupFig.4Fig.5.Fig.61.Limbischemicpostconditioningprotectsmyocardiumfromischemia-reperfusioninjury.

ScandCardiovascJ.2006Oct2.TRPV1activationisinvolvedinthecardioprotectionofremotelimbischemicpostconditioninginischemia-reperfusioninjuryrats.BiochemBiophysResCommun.2015Aug73.RemoteIschemicPost-ConditioningI