腺苷A_1受体激动剂对兔心肌缺血－再灌注一氧化氮及其合酶基因表达的影响

EfectofadenosineA1receptoragonistR┐PIAonnitricoxideproductionandmRNAofnitricoxidesynthaseinmyocardialischemia┐reperfusioninrabbits

为观察腺苷Ａ１受体激动剂Ｒ－苯异丙基腺苷对心肌缺血－再灌注期一氧化氮产物（ＮＯＰ）及一氧化氮合酶（ＮＯＳ）基因表达的影响，１５只新西兰兔随机分为三组：Ⅰ组左前降支（ＬＡＤ）缺血１０分钟，再灌注９０分钟；Ⅱ组ＬＡＤ缺血前１５分钟给予Ｒ－ＰＩＡ（０．３ｍｇ／ｋｇ）静脉注射；Ⅲ组Ｒ－ＰＩＡ静脉注射前给予选择性腺苷Ａ１受体拮抗剂ＤＰＣＰＸ（１．０ｍｇ／ｋｇ）静脉注射。结果显示，给Ｒ－ＰＩＡ后血ＮＯＰ水平迅速上升达近２倍于基础值，且在缺血－再灌注期始终高于基础值，同时伴心率（２７．６％）和血压（２０％）的下降。先给ＤＰＣＰＸ可消除上述作用。Ｎｏｒｔｈｅｒｎ杂交结果显示，Ⅱ组缺血心肌ＮＯＳｍＲＮＡ表达增强。结果认为：Ｒ－ＰＩＡ可以引起ＮＯＰ升高并减少其在缺血期及再灌注早期的下降，其机制可能与ＮＯ生成及ＮＯＳ增多有关。

TheaimofthisstudywastotesttheefectofadenosineA1receptoragonistR-PIAonendogenousnitricoxideproducts(NOP)andtheexpressionofnitricoxidesynthase(NOS)geneinmyocardialischemiaandreperfusioninanesthetizedrabbits.Myocardialischemiawasinducedbyliga-tionofLADarteryfor10-minfolowedby90-minofreperfusion(groupI,n=5).R-PIA(0.3mg/kg)wasinfusedi.v.for5minstarting15minbeforeLADocclusion(groupⅡ,n=5).AselectiveadenosineA1receptorantagonistDPCPX(1.0mg/kg)wasinfusedi.v.for5minstarting15minbe-foreR-PIAinfusion(groupII,n=5).ThebloodlevelsofNOP(nitrite)weredeterminedbymodi-fiedGreissmethodatbaseline,5,10minafterdruginfusionsandLADocclusion,5,10,30,60,90minafterreperfusion.TheexpressionofNOSgeneinischemicareaofthemyocardiumwasstudiedbyNorthernblotinthethreegroups.ThelevelsofNOPat5minafterR-PIAinfusionrapidlyin-creasedtotwicethebaseline(1.15±0.28μmol/Lto2.16±0.42μmol/L,P<0.05)andcontinuedtobehigherthanthebaselineduringischemiaandreperfusionaccompaniedbydecreasesofheartrateby27.6%andbloodpressureby20%.AloftheaboveefectswereabolishedbypriorinfusionofDPCPX.NorthernblotshowedthattheNOSmRNAexpressionincreasedingroupIcomparedwiththoseingroupIandII.R-PIAinfusionincreasedthebloodlevelofNOPandatenuateditsdecreaseduringischemiaandtheearlystageofreperfusion,themechanismofwhichismostprobablyduetothestimulationofadenosineA1receptorandtheincreaseofNOS.