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褪黑素通过抑制细胞焦亡保护NMP保存的DCD心脏机制研究.docx

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褪黑素通过抑制细胞焦亡保护NMP保存的DCD心脏机制研究 Title:MechanismsofMelatonin-mediatedProtectionofNMP-preservedDCDHeartsbyInhibitingCellularApoptosis Abstract: Donationaftercirculatorydeath(DCD)hasemergedasavaluablesourceofdonorheartsfortransplantation,potentiallyexpandingthepoolofavailableorgans.However,ischemia-reperfusioninjuryduringpreservationandtransplantationleadstoahighincidenceofprimarygraftdysfunction.Melatonin,ahormoneproducedbythepinealgland,hasbeenproposedasapotentantioxidantandcellprotectant.ThisstudyaimstoinvestigatethemechanismsthroughwhichmelatoninprotectsDCDheartspreservedinnormothermicmachineperfusion(NMP)byinhibitingcellularapoptosis. Introduction: DCDhearttransplantationisapromisingapproachtoaddresstheshortageofdonororgans.However,theischemicinjuryoccurringduringpreservationandreperfusionleadstosignificantoxidativestressandcelldeath.Melatoninhasbeenshowntopossessimportantantioxidantandanti-apoptoticpropertiesandcanmitigatetheischemia-reperfusioninjuryinvariousorgans,includingtheheart.Thus,understandingthemechanismsofmelatonin-mediatedprotectioninDCDheartsiscriticaltoimprovingpreservationandtransplantationoutcomes. Methods: 1.ProcurementofDCDhearts:HeartsfromDCDdonorswereprocuredusingastandardizedprotocol. 2.Normothermicmachineperfusion(NMP):HeartswerepreservedusingNMP,whichprovidesaphysiologicalenvironmenttosupportheartfunctionandsimulatetransplantation. 3.Experimentalgroups:Heartsweredividedintothreegroups:control,melatonin-treated,andmelatonin+apoptosisinhibitor-treated. 4.Functionalassessment:CardiacfunctionwascontinuouslymonitoredduringNMPusingpressure-volumeloopanalysisandechocardiography. 5.Biochemicalanalysis:Markersofoxidativestress,mitochondrialfunction,andapoptosiswereevaluatedusingvariousassays. 6.Histology:Tissuesectionswerestainedandexaminedtoassessmyocardialdamageandapoptosis. Results: 1.Melatoninimprovedfunctionalrecovery:HeartstreatedwithmelatoninexhibitedsignificantlyimprovedcardiacfunctioncomparedtothecontrolgroupduringNMP. 2.Attenuationofoxidative