磷酸二酯酶抑制剂的药理及临床应用进展

,(,313000):,,,,,:;;;PharmacologyandapplicationprogressofthephosphodiesteraseinhibitorLIXiao2ming,HUAi2hong(DepartmentofPharmacy,TheFirstPeoplesHospital,Huzhou,ZhejiangProvince313000,China)Abstract:Theauthorshavedonetheresearchbyconsultingtherelativedomesticphosphodiesteraseinhibitorliteraturepublishedinre2centyears.Attemptshavebeenmadetoknowthestatwsquoofthephosphodiesteraseinhibitorclinicalpracticeinrecentyears.Ananaly2sisofitsfunctionalmechanismhasbeenmade,forfurtherdevelopment.Theresearchesshowthatphosphodiesteraseinhibitorhasdifferentfunctionsinclinicalpracticebecauseofphosphodiesteraseisoenzymetypedifference,distributiondifferenceandselectivedifference,etc.Selectivephosphodiesteraseinhibitormaybeusedtotreatmanykindsofdiseases,andhasbeenthehotspotinbeingappliedtode2velopingcardiacagents,vasodilatationmedicine,muscle2smoothingdiastolemedicine,antiasthmaticmedicine,anti2despondentmedi2cine,etc.Keywords:phosphodiesteraseinhibitor;selectivity;heartfailure;sexualimpotence(PDEs)11[1],PDEs,,PDE3,,,;PDE4;PDE5(Sildenafil)/(NO/cGMP),1(cAMP)(cGMP),,()(PDEs)PDEs3,52,cGMPcAMP52,22.1PDE3PDE3PDE3,1030,,cAMPPDE3,cAMP52AMP,cAMPcAMPCa2+,,,cAMP,,,,PDE3,,,(PES)2(VES)(dp/dtmax)2(VED)(SW)2VED,,,/(EES/Ea),,,,,,[2],PDE3,cAMP[3],[4],[5,6],,,,,,,,,PDE3A,PDE3A,cAMP,,,,,,,464AnhuiMedicalandPharmaceuticalJournal2006Jun;10(6)©1994-2011ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.()[7]2.2PDE4PDE4,[8](M)(EOS)PDE4,,PDE4PDE44[9],PDE4APDE4BPDE4CPDE4D,,4D4B3,PDE4Zaprinast,(Rolipram),Ro2021724RolipramPDE4,,RolipramRo2021724B4PDE4,Rolipram,,(Piclamilast)PDE4,,Rolipram,Piclamilast,[10],PDE4,,:,,[11]PDE4:/,Th22425(),,26,,,G2arrestin22PDE4,,PDE4,,,,PDE4,,[12]PDE4[13]2.3PDE5PDE5,cGMP,PDE53,[14],19983,FDAPDE5(Sildenafil)[15],,,,,PDE5[16],(NANC)NANC,NONANC,NANC,NOL2NO,,,(GC),,NO2GC,GC,cGMP,cGMP,,cGMPPDE552GMPSildenafilPDE5cGMP,cGMP,,,sildenafilNO,,cGMP,cGMP,sildenafil,cGMP28[8]NONANC[17],(PE),,116Hz,SildenafilPE,Sildenafil,SildenafilNO,NO/cGMP(MCH)PE,SildenafilMCHSil2denafilNO,NO/cGMP[8],,Sildena2fil3PDEs,,PDE,,PDEsPDEsPDE,PDE,,PDEs,,,,564AnhuiMedicalandPharmaceuticalJournal2006Jun;10(6)©1994-2011ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(,116021):;(FattyLiver,FL),(Triglyceride,TG),TG100g45g,50%,20%,7%,5%,1/3,[1],,,10%,50%,5715%,5.2%11.4%,,,,,,,25%,1.5%8.0%[2],,,,,,[3],[4],11.1,[5,6]:(FFA),TG;2,,TG;(VLDL),TG;FFA1.2,,,,,,,VLDL,,,:[1]RachaelB,GeorgeS.BaillieDifferentialexpressionofPDE4cAMPphosphodiesteraseisoformsininflammatorycellsofsmokerswithCOPD,smokerswithoutCOPD,andnonsmokersAmJPhysiolLungCellMolPhysiol,2004,287(2):332-43.[2],,.[J].,2003.6.(3):399-400.[3],.[J].,2003,38:675-7.[4],.[J].ChineseJournalofPathophysiology,2003,19(7):875-88.[5].[J].,2002,8:510-2.[6].[J].,2002,21(11):683-5.[7],,.[J].,2004,8(18.):3523-5.[8],,.[J].,2000,16(.2):121-4.[9],,.[J].,2002,21(5):303-7.[10],,.[J].(),2003,32,(4):274-8.[11],.[J].,2003,12:947-9.[12],.[J].,2004,24(6):404-9.[13],.[J].,2004,15(5):310-2.[14],.PDE5[J].,2005,11,(7):552-5.[15],,..[J].:,2003,30(4):235-6.[16],.5[J].,2005,8:631-4.[17],.[J].,2002,11(12):914-7.(:2006-02-22)664AnhuiMedicalandPharmaceuticalJournal2006Jun;10(6)©1994-2011ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.