高原红细胞增多症及药物防治

高原红细胞增多症及药物防治(830063):(highaltitudepolycythemia,HAPC):15:(erythropoietin;EPO)HAPC,(adenosine;AD)EPO;RBCRBC,EPO,HAPC;HCTEPO,PaO2SaO2;AD,EPORBC,;,:HAPC/EPO;ADHAPC;R594.33000m,,HAPC:RBC6.5!1012/L,HB200g/L,HCT65%(PaO2),(PaCO2)X,,,,HAPC,HAPC,HAPC1HAPC1.1EPO,50EPO,(cobalt),EPOEPO,,[1210]EPO,EPO,[12]EPO34000D(Daltons),24000D,30%~35%160000U,EPO165,V-8C(endoproteinase),(disulfidebridges)EPO(31%)(24%);(fucose)N-N-(N-acetylneuraminicacid),EPO/EPO,()EPO,,/EPOEPO∀#(hemeprotein),∀#∀#,EPOmRNA,∀#,,EPO[1~10]EPOmRNA,EPOEPOmRNA,EPO582007174EPOmRNAEPOCOS-7,EPO5∃-3∃-,,EPO,RBC,HAPC[34],ATPADPAMP,5∃-AD,11EPO6KPGE1:6-E1;2-AdAg:2;GS:G;AC:(FisheJW.AmRerpharmacol.Toxicol1988,28:101~22)ADEPO,:%ADEPO;&ADEPO;∋ADA1A2(A2,AC,cAMP)(A1,AC,cAMP)EPOA,A2,EPO/[1]AD,EPO/,ACTH5-(cAMP,11.2HAPCRBC,RBC[1112][13](3600~4700)mHAPC27,RBC,ATPase,;Na+-K+ATPaseCa2+-ATPaseMg2+-ATPase,HCTHB,,HAPCRBCNa+K+Ca2+[14]5000m,,PeacockRBC(spectrin),BL88-CRBC,41,,RBCRBC,,RBC,RBC,,HAPC∀#[14~16]1EPOcAMP(2-ACTH(PGE1,PGE2,PGI2,6K-PGE1)()A25-()A2N∃-N-5--(1)5920071741.3EPOHAPC2%,,HAPCEPO,,,,HAPCEPO[9],EPO,,,EPO,RBC,EPOMongeC(1992)HAPCHB,,EPO,EPO,EPOmRNA6,3,EPO,EPO,EPORBC[12],,EPO[910]HAPC,7296120,[1718],HAPC1.4HAPC,,:%(PAIFDP),[19~24];&)(AT-))[20~24];∋(Tissuefactor,TF)[21~24]TF/,),,,[21~23]TF,TF,TFA2(TXA2),,(EC-304),TXA2TXA2[25~27],HAPCHAPC,,,HAPC[28]2HAPCHAPC,,,,,,2.12.1.1(Angiotensinconvertingenzymeinhibitors;ACEI)(enalapril)(Captopril)GastonRS,EPOHAPC,ACEI,HCTHB,,ACEIHAPC[29~33]PlataR[34],26HAPC,HCT55%,24150mg13,,5mg/,213,2/,;HCT(63.5%56.8%)HB(207g/L164g/L)(358.6mg247.7mg/24h)(P0.0001P0.002)HCTHB24h(P0.0001)BomanKO[35],,[36],25mg/,3,72:(A)35();(B)3720(C):A(tissueplasminogenactivator;tPA)[(0.40∗0.14)!103IU/L(0.58∗0.13)!103IU/L](P0.010.05),(plasminogenactivatorinhibitor-1;PAI-1)[602007174(6.6∗1.8)!103AU/L(4.9∗1.5)!103AU/L](P0.010.05)BtPAPAI-1,AtPAPAI-1,,B,,HAPCACEI,,HAPCACEIHAPC,,ACEI(,,,,EPO,HAPC;,HAPC[33];,N----(N-acetyl-seryl-aspartyl-lysyl-proline;NASALP),,ACEI,,RBC[37],ACEI,((AT1;AT2),:(losartan)AT1,,,,,HAPC2.1.2(Acetazolamide;ACZ),,H+H+-Na+,Na+,,,;,,/EPO,HAPCRichaletJP[38]4300m30,ACZ250mg/(qd!3)ACZ500mg/(qd!3),10:ACZHCT7.1%6.7%(P0.001);EPO67%(P0.01)50%(P0.001);(solubletransferringreceptors)11.1%(P0.05)3.4%(P0.001),ACZ5%(P0.01),11%(P0.05),74%(P0.05)EPOACZACZHAPC,,,(antisterone),,HAPC,,,[3940]2.1.3[1941])(antithrombin);AT)),,+a,a−a.a,,HAPCAT),AT)(aspirine),,ADPTXA2,,(40~80)mg,(2~3)(ridogrel),TXA2TXA2,,,2.1.4[942~44]ADEPOADA1A2,AC-cAMP-,EPO(theophyllines),,AD,EPO,RBC,HAPC;,cAMP,,HAPC2.22.2.1,HAPC[404546],,:%,,;&;∋,2.2.1.1(foliumginkgo)612007174(ginkgobilobaL)2.5%~5.91%,35,17,6,75,,(ginkgolideABCMJ5)(bilobalide),(PAF)PAF,[47~49]HAPC,101800m5200m,80mg,2,,41%,120mg,2,60mg3,HAPC,[49~52]2.2.1.2[53],(3600~4370)m,HAPC112(109,3),34.6,33300.5g,3,30,tPAPAI-1,(FG)(FDP),HAPCt-PAPAI-1FGFDP(P0.01),t-PAPAI-1FGFDP(P0.01)HAPC,2.2.2HAPC∀#∀#∀,#,∀,,#,,HAPC[54]HAPC,[55],,2.2.2.1[56]6∀#(:20025866),,HAPC:10,;67,,(SOD)(GSH-Px):%310,HBRBC;&129HAPC,83%;HB(220.8∗17.4)g/L(185.6∗18.5)g/L(P0.01),RBC(7.49∗0.94)!1012/L(6.09∗1.18)!1012/L(P0.010.05),HCT(68.7∗3.4)%(56.0∗5.1)%(P0.05)35HAPC,PaO2SaO2(P0.01);40,,(P0.01)∋2520,(P0.01),HAPCHAPC2.2.2.2[57](10g)(5g)10mL,4475m,15mL/(kgd),1,9TXA2(P0.05),TXB2(TXA2)(P0.01)6--F1,,,(P0.05)TXA2HAPC,TXA2TXA26--F1,∀#2.2.2.3,()[58],622007174103700m15,,SOD,MDA(P0.01)3HAPCEPO,ACEIAT-(ADHAPCACZ,,,,,HAPC,1FisherJW,NakashimaJ.Theroleofhypoxiainrenalproductionoferythropietin.Cancer(suppl)1992,70(4):928~39.2WestJB.Thephysiologicbasisofhighaltitudediseases.AnnInternMed,2004,141(10):789~800.3MiyakeT,kungCK-H,GoldwasserE.Purificationofhumanerythropoietin.JBiolchem,1977,252:5558~64.4LinF-K,SuggsS,LinCH.Cloningandexpressionofthehumanerythropoietingene.ProcNatlAcadSciUSA,1985,82:7582~4.5GoldwasserE,JacobsonLD,FriedW,etal.Mechanismoftheerythropoietineffectofcobalt.Science,1957,125:1085~6.6PauloLG,FinkGD,RohBL,etal.EffectsofseveralandrogensandsteroidmetabolitesonerythropoietinproductionintheisolatedPerfuseddongkidney.Blood,1974,43:39~47.7FisherJW,SamuelsAI,LangstonJW.Effectsofangiotensinandrenalarterycontrictiononerythropoietinproduction.JPharmacolExpTher,1967,157:618~25.8UenoM,BrookinsJ,BeckmanB,etal.A1andA2adenosinereceptorregulationoferythropoietinproduction.LifeSei,1988,43:229~37.9NakashimaJ,BrookinsJ,BeckinonB,etal.IncreasederythropoietinsecretioninhumanhepatomacellsbyN/-cyclohexyl-adenosine.AmJPhsiol,1991,261:455~60.10,,..,1997,7(4):57~9.11PearsonT.Na+-K+ATPaseofculturemusculardystrophyerythrocyteghosts.Lifescience,1978,2:127~9.12YeaglePL.CholesterolmodulationofNa+-K+ATPase.ATPhydrolyzingactivityinthehumanerythrocyte.BiochemicaBioPhysActa,1983,727(1):39~45.13,,,..,1998,8(3):12~3.14,,,..,1997,7(2):8~10.15DoyleMP,WalkerBR.Stiffenederythrocytesaugmentthepulmonaryhemodynamicresponsetohypoxia.JApplephyiol,1990,69:1270~5.16MohandasN,ChasisJA.Redbloodcelldeformability,membranematerialpropertiesandshape:Regulationbytransmembrane,skeletalandcytosolicproteinsandlipid.seminHematol,1993,30:171~7.17,,,..,2003,13(1):9~10.18..,2003,24(2):4~6.19RupertJL,MonsalveMV,KiddKK,