心肌缺血再灌注损伤的主要机制与相关药物治疗的研究进展-徐盟

2014－02－202009110001、、。。、、。MIＲI。MIＲI/TNF-αＲesearchonmainmechanismsofMIＲIandrelateddrugtherapyXUMengChinaMedi-calUniversityShenyang110001ChinaAbstractIschemia-reprefusioninjuryIＲIoftenoccurredafterischemiamyocardialistreated．WhenIＲIoc-curredthedamagingdegreeofmyocardialaggravatedandinfarctionareaexpanded．Thephenomenonisassociatedwithavarietyofmechanismsincludingoverloadingcalciumincreasedoxygenfreeradicalsinflammationetc．Withtheim-provementofMIＲI’streatingtechnologytreatmentsduringMIＲIbecomeakeytotreatischemiamyocardial．Sore-searchofdrugsforpreventingortreatingdiseaseduringMIＲIhasbecomethekeypoint．Commonmechanismsofdrugsincludereducingcalciumoverloadedanti-inflammationresistingoxygenfreeradicalsandimprovingenergymea-tabolismetc．ThisarticleaimstosummarizedifferentpathologicmechanismsofMIＲIandrecentresearchofrelateddrugs．KeywordsMIＲINCXOFＲInflammationfactorTNF-α0。Myocardialischemia-reprefusioninjuryMIＲI。MIＲI、、、、1。MIＲI。。11.1MIＲI、。。、ATP、2。MIＲI。。。/。/NCXNCX、、。ATPpHpH·2501·2014178PracticalPharmacyAndClinicalＲemedies2014Vol．17No．8/NHE。NCX。ⅡCa2+/calmodulin-dependentkineaseⅡCaMKⅡCaMKⅡδKOmiceCaMKⅡδＲyＲ23。L、。1.21.2.1NCXNCXATP31。NHENCX。NCXMIＲI。NCXNCX。El-Ani4NCX/。NCXMI-ＲI。NCXSEA04005。NCX。1.2.2NHENHENCXNHE。pHpHNHENCX。Liu6NHEHOE694MIＲI。Jung7NHEKＲ-32570MIＲI。Inserte8cGMP/PKGNHE。NHEMI-ＲI。22.1MIＲI。5%、、、OFＲ。OFＲOFＲ、。OFＲ。MIＲIOFＲ。MIＲIOFＲ-、、、。OFＲ、。2.2OFＲ。OFＲ①SOD、CAT、GSH-PX。②A、E。GSHⅡNADPH。。MIＲIOFＲOFＲOFＲ。。。·3501·2014178PracticalPharmacyAndClinicalＲemedies2014Vol．17No．8STMIST113%9。N-NACGSH。。EdaravoneMCI-186OFＲOFＲ。。MCI-186。。。MDASODGSH-PX10。SB209995SB211475。SB209995SB211475。。。33.1MIＲIpHpH。ATPNa+-K+-ATP。。ATPCa2+-ATP。XDHOFＲ。。3.2ATPMIＲI。TMZ11MIＲI12。TMZMIＲI。TMZMIＲI13。TMZMIＲIMIＲI14。TMZMIＲI。44.1MIＲI。MIＲI。。κBNuclearfactor-κBNF-κB、TNF-α、1Highmobilegroupbox1proteinHNGB1、IL-6。TNF-αMIＲINF-κBNF-κBTNF-α。TNF-α、。MIＲITNF-αＲOS。TNF-αAMI—15。MIＲITNF-α16。MIＲI8dTNF-·4501·2014178PracticalPharmacyAndClinicalＲemedies2014Vol．17No．8αTNF-α。TNF-αMIＲITNF-α17。。。。4.2MIＲI。。IL-618。。、。Ⅱ。ＲAASⅡ19。ＲAASⅡ。Ⅱ。。5MIＲI。、、MIＲI、p38MAPK、。MIＲI。MIＲI。1TurerATHillJA．Pathogenesisofmyocardialischemia-reper-fusioninjuryandrationalefortherapyJ．AmJCardiol20101063360-368．2GomezLLiBMewtonNeta1．InhibitionofmitochondrialpermeabilitytransitionporeopeningtranslationtopatientsJ．CardiovascＲes2009832226-233．3．-J．2013103156-158．4El-AniDStavHGuettaVetal．Ｒapamycinsirolimuspro-tectsagainsthypoxicdamageinprimaryheartculturesviaNa+/Ca2+exchangeractivationJ．LifeSci2011891-27-14．5NamekataIShimadaHKawanishiTetal．ＲeductionbySEA0400ofmyocardialischemia-inducedcytoplasmicandmi-tochondrialCa2+overloadJ．EurJPharmacol20065431-3108-115．6LiuHCalaPMAndersonSE．Na/Hexchangeinhibitionpro-tectsnewbornheartfromischemia/reperfusioninjurybylimit-ingNa+-dependentCa2+overloadJ．CardiovascPharmacol2010553227-233．7JungISLeeSHYangMKetal．CardioprotectiveeffectsofthenovelNa+/H+exchanger-1inhibitorKＲ-32560inaper-fusedratheartmodelofglobalischemiaandreperfusionIn-volvementoftheAkt-GSK-3betacellsurvivalpathwayandan-tioxidantenzymeJ．ArchPharmＲes20103381241-1251．8InserteJBarbaIPoncelas-NozalMetal．cGMP/PKGpath-waymediatesmyocardialpostconditioningprotectioninratheartsbydelayingnormalizationofintracellularacidosisduringreperfusionJ．MolCellCardiol2011505903-909．9ＲentoukasETsarouhasKTsitsimpikouCetal．Theprognos-ticimpactofallopurinolinpatientswithacutemyocardialin-farctionundergoingprimarypercutaneouscoronaryinterventionJ．IntJCardiol20101452257-258．10．J．200711039-40．11．J．2013891214-1215．·5501·2014178PracticalPharmacyAndClinicalＲemedies2014Vol．17No．812．J．200836136-39．13．J．2013154457-460．14LiJJ．InflammationincoronaryarterydiseasesJ．ChinMedJEngl2011124213568-3575．15XiaoHChenZLiaoYeta1．Positivecorrelationoftumornecrosisfactor-alphaearlyexpressioninmyocardiumandven-triculararrhythmiasinratswithacutemyocardialinfarctionJ．ArchMedＲes2008393285-291．16MoroCJouanMGＲakotovaoAeta1．Delayedexpressionofcytokinesafterrepeffusedmyocardialinfarctionpossibletrig-gerforcardiacdysfunctionandventricularremodelingJ．AmJPhysiolHeartCircPhysiol20072935H3014-H3019．17．/J．2011323332-337．18．-J．2012352100-102．19．PPAＲγJ．2005215872-875．2013－12－1711000120081050**PEG-ASPL-ASPALL。L-ASP。PEG-ASP、、。Ｒesearchprogressofpegaspargaseinthetreatmentofchildrenwithacutelympho-cyticleukemiaYANHongHELi*DepartmentofPediatricsFirstAffiliatedHospitalofChinaMedicalUni-versityShenyang110001ChinaAbstractPegaspargasePEG-ASPisthepolyethyleneglycolPEGconjugationofL-asparaginaseoneofthefirst-linedrugsinthetreatmentofacutelymphocyticleukemiaALLforchirdren．ComparedwiththeL-ASPPEG-ASPreducesantibodyformationextendshalf-timedecreasestheincidenceofallergicreactionswhilemaintainingL-ASP'sactivity．InthispapertheprogressonthepharmacokineticsdrugresistanceclinicalapplicationandsafetyofPEG-ASParereviewed．KeywordsPegaspargaseAcutelymphocyticleukemiaChildren0ALL75%～80%1。L-ASPALLALL80%2。L-ASP、、、、3。PEG-ASP。PEG-ASPPEGL-ASPL-ASPL-ASP20h5.5dL-ASP54-5L-ASP6。PEG-ASPL-ASP7。1984PEG-ASP1994FDAL-ASPALL2006FDA·6501·2014178PracticalPharmacyAndClinicalＲemedies2014Vol．17No．8