Upregulation of the pro-apoptotic genes BID and FAS in septic shock patients 英文参考文献.docVIP

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Upregulation of the pro-apoptotic genes BID and FAS in septic shock patients 英文参考文献.doc

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Upregulation of the pro-apoptotic genes BID and FAS in septic shock patients 英文参考文献

Turrel-Davinetal.CriticalCare2010,14:R133 /content/14/4/R133 RESEARCH OpenAccess Upregulationofthepro-apoptoticgenesBIDand FASinsepticshockpatients FannyTurrel-Davin1,CarolineGuignant2,AlainLepape1,3,BrunoMougin1,GuillaumeMonneret1,2, FabienneVenet2* Abstract Introduction:Lymphocyteapoptosishasbeensuggestedtoplayacentralroleinsepsispathophysiology,and studiesinanimalmodelsdemonstratedthatblockingthispathwayimprovesoutcome.However,noroutine biomarkersofapoptosisaresofaravailableinpatients.Thus,theaimofourstudywastoassessthedifferent biomarkersofapoptosisputativelyusableonaroutinebasisinsepticshock. Methods:Thirteensepticshockpatients(sampledtwicebetweendays1to2anddays3to5afterdiagnosisof shock)and15sex-matchedandage-matchedhealthycontrolswereprospectivelyenrolled.Apoptosiswas measuredinlymphocytesubpopulationsusingflowcytometry(Annexin-Vbinding,activatedcaspase-3andBcl-2 expressions).Representativepro-apoptoticandanti-apoptoticgeneexpressionswereassessedbyquantitative reverse-transcriptionPCR.MonocyteHLA-DRexpressionandlymphocytesubpopulationcellcountsweremeasured asmarkersofsepsis-inducedimmunedysfunctions.Totestforstatisticalsignificance,theMann-WhitneyUtestwas usedwithcorrectionbythenumberoftestsperformed. Results:FlowcytometricmeasurementsofapoptosisinsepticshockpatientsshowedanincreasedAnnexin-V bindingonCD4+ Tcellsandanincreasedactivecaspase-3expressiononBcellsonlyatdays3to5(sixfold changeandtwofoldchange,respectively).GeneexpressionanalysisshowedanincreasedBCL-XLmRNAandan upregulationofthepro-apoptoticgenesBIDandFASinsepticshockpatients(10-foldchangeandfivefoldchange, respectively)comparedwithhealthycontrols. Conclusions:Thepresentstudyhighlightsthedifficultiesencounteredinmonitoringapoptosisonaroutinebasis insepticpatients,whereasinthesamesamplingconditionsandonthesamepatients,HLA-DRexpressionand lymphocytesubpopulationcellcountsshowedcharacteristicsdescribedintheliterature.However,pro-apoptotic genesBIDandFASappeartoconstitutepromisingapoptosismarkersinou