不对称二甲基精氨酸在冠心病临床分型中的应用

不对称二甲基精氨酸在冠心病临床分型中的应用中南大学学版2O1O,354HTTP/XHYXYSMNELJCENTSOUTHUNIVMEDSCI一3O1CORRELATIONBETWEENPLASMAASYMMETRICDIMETHYLARGININEANDDIFFERENTTYPESOFCORONARYHEARTDISEASECAOYU,YANGKAN,ZHANGZHIHUI,OUYANGMAO,XIAOLIDEPARTMENTOFCARDIOLOGY,THIRDXIANGYAHOSPITAL,CENTRALSOUTHUNIVERSITY,CHANGSHA410013,CHINAABSTRACTOBJECTIVETOMONITORTHECHANGESOFPLASMAASYMMETRICDIMETHYLARGININEADMA,NITRICOXIDENO,ANDVONWILLEBRANDFACTORVWFLEVELSINPATIENTSWITHSTABLEANGINAPECTORISSAPORACUTECORONARYSYNDROMEACSANDTOEVALUATETHECORRELATIONBETWEENADMAANDDIFFERENTTYPESOFCORONARYHEARTDISEASEMETHODSATOTALOF143SUBJECTSWEREDIVIDEDINTOANONCHDGROUP,ASAPGROUPANDANACSGROUPPLASMALEVELSOFADMANOANDVWFWEREEXAMINEDANDTHEIRCORRELATIONWITHSAPORACSWASANALYZEDRESULTSCOMPAREDWITHTHENONCHOORTHESAPGROUP,ADMALEVELWASELEVATEDINTHEACSGROUPP005THEADMALEVELTENDEDTOINCREASEINTHESAPGROUPCOMPAREDWITHTHENONCHDGROUP,BUTHADNOSIGNIFICANTDIFFERENCEP005COMPAREDWITHTHENONCHDGROUP,NOLEVELWASDECREASEDINBOTHTHESAPANDACSGROUPP005,ANDITDECREASEDMOREINACSGROUPTHANTHATINTHESAPGROUPP005VWFLEVELSWEREINCREASEDINBOTHTHESAPANDACSGROUPCOMPAREDWITHTHENONCHDGROUPP005THEREWASNOSIGNIFICANTDIFFERENCEINTHEPLASMALEVELSOFVWFINTHESAPANDTHEACSGROUPP005CONCLUSIONTHECHANGEOFPLASMAADMALEVELISCLOSELYCORRELATEDWITHACUTECORONARYSYNDROMEADMAMIGHTBEACLINICALMARKERFORACUTECORONARYSYNDROMEKEYWORDSASYMMETRICDIMETHYLARGININENITRICOXIDECORONARYHEARTDISEASEACUTECORONARYSYNDROME不对称二甲基精氨酸在冠心病临床分型中的应用曹宇,杨侃,张志辉,欧阳茂,肖丽中南大学湘雅三医院心血管内科,长沙41O013摘要目的测定冠心病患者中稳定型心绞痛和急性冠脉综合征的血浆不对称二甲基精氨酸ADMA,一氧化氮NO和血管性血友病因子VWF水平,探讨其与冠心病各临床类型之间的关系方法按纳入与排除标准入选了143例研究对象,其中包括非冠心病组64例,急性冠脉综合征组54例和稳定性心绞痛组25例检测各组血浆ADMA,NO和VWF水平,并分析它们与急性冠脉综合征和稳定性心绞痛之间的相关性结果与非冠心病组和稳定型心绞痛组比较,急性冠脉综合征血浆ADMA水平显着升高P005与非冠心病组相比,稳定型心绞痛组血浆ADMA水平有升高趋势但差异无统DATEOFRECEPTION20090602BIOGRAPHYCAOYU,MASTERDEGREE,MAINLYENGAGEDINTHEINTERVENTIONALCARDIOLOGYANDPATHOGENESISOFCORONARYHEARTDISEASECORRESPONDINGAUTHORXIAOLI,EMAILCAOYUXIAOLIHOTMAILCON中南大学医学版,2010,354HTTP/XBYXXYSMNET计学意义尸005与非冠心病组相比,稳定型心绞痛和急性冠脉综合征组血浆NO水平均显着下降P005,急性冠脉综合征组下降的程度明显大于稳定型心绞痛组P005与非冠心病组相比,稳定型心绞痛组和急性冠脉综合征组血浆VWF水平均显着升高P005稳定型心绞痛组和急性冠脉综合征组之间血浆VWF水平差异无统计学意义P005结论血浆ADMA水平变化与冠心病中急性冠脉综合征的发生发展密切相关,血浆ADMA水平的变化可能是急性冠脉综合征的预测因子关键词不对称二甲基精氨酸一氧化氮冠心病急性冠脉综合征DOI103969/JISSN16727347201004004ENDOTHELIUMDERIVEDNITRICOXIDENO,WHICHPOSSESSESVARIOUSBIOLOGICALPROPERTIESSUCHASANTIOXIDATION,ANTIINFLAMMATIONANDANTIAPOPTOSISPLAYSANIMPORTANTROLEINMAINTAININGTHEINTEGRITYOFBLOODVESSELENDOTHELIUMANDPREVENTINGTHEDEVELOPMENTOFATHEROSCLEROSISINTHEDEVELOPMENTOFCORONARYHEARTDISEASECHD,IMPAIREDFUNCTIONOFBLOODVESSELENDOTHELIUMISCLOSELYRELATEDTOTHEDECLINEOFNOLEVELINPLASMATHEGENERATIONOFNOISFROMLARGININECATALYZEDBYNOSYNTHASESNOSRECENTLY,ITWASREPORTEDTHATLARGININEANALOGUEASYMMETRICDIMETHYLARGININEADMA,AMAJORENDOGENOUSINHIBITOROFNOS,PLAYSACENTRALROLEINREGULATIONOFNOSYNTHESIS,ANDTHEPLASMALEVELOFADMASIGNIFICANTLYINCREASEDANDACCOMPANIEDBYTHEDECREASEDNOLEVELSINCHDPATIENTS,SUPPORTINGTHATADMAWASANOVELINDEPENDENTRISKFACTORFORCHDCHDPATIENTSARECLASSIFIEDAS2TYPESINCLINIC,STABLEANGINAPECTORISSAPANDACUTECORONARYSYNDROMEACSAHHOUGHTHEPOSITIVECORRELATIONBETWEENCHANGESOFPLASMAADMALEVELANDTHEOCCURRENCEOFCHDHASBEENPREVIOUSLYREPORTED,THECORRELATIONBETWEENTHECHANGESOFPLASMAADMALEVELANDDIFFERENTTYPESOFCHDSREMAINSLARGELYUNKNOWNINTHISSTUDY,CHDPATIENTSWERECLASSIFIEDASACSANDSAPGROUPSACCORDINGTOCLINICALSYMPTOMSBYMEASURINGANDANALYZINGTHECHANGESOFPLASMAADMANOANDENDOTHELIALACTIVATINGFACTORVWFLEVEL,WEEVALUATEDTHECORRELATIONBETWEENADMAANDDIFFERENTTYPESOFCHDS,ORTHEDEGREEOFATHEROSCLEROTICSTENOSIS11SUBJECTSWECHOOSE143PATIENTSACCEPTINGSELECTIVEEOYONARYANGIOGRAPHY,79PATIENTSWITHATHEROSCLEROSISASACHDGROUPAND64PATIENTSWITHOUTCORONARYATHEROSCLEMSISASANONCHDGROUPWHOWEREFROMTHEDEPARTMENTOFCARDIOLOGYINTHETHIRDXIANGYAHOSPITALDUETOCHESTPAIN,CHESTTIGHTNESS,ANDPALPITATIONFROMOCTOBER2006TOOCTOBER2007THECHDGROUPWASFURTHERDIVIDEDINTOAACSGROUP54PATIENTSANDASAPGROUP25PATIENTSASACCORDINGTOCLINICALSYMPTOMSINCLUSIONCRITERIATHEPATIENTSWEREINQUIREDFORHISTORYOFDISEASESANDACCEPTEDPHYSICALEXAMINATIONS,ANDMEANWHILECOMPLETEDEXAMINATIONSINCLUDINGBLOODROUTINE,LIVERANDKIDNEYFUNCTION,ELECTROCARDIOGRAMECGANDSELECTIVECORONARYANGIOGRAPHYWITHOUTLIMITSONANTIDIABETESANDANTIHYPEFLIPIDENMIATHERAPYBEFOREBEINGCHOSENEXCLUSIONCRITERIA1SEVEREINFECTIOUSDISEASESORCHRONICINFLAMMATORYDISEASESLASTMONTH,INCLUDINGSEVEREUPPERRESPIRATORYTRACT,LUNG,ANDHEPATOBILIARYDUCTINFECTION2ACTIVETUBERCULOSIS3SURGICALOPERATIONORTISSUETRAUMARECENTLYWITHIN3MONTHS4SEVEREDAMAGEDLIVERORKIDNEYFUNCTIONS5MALIGNANTTUMOR6CONNECTIVETISSUEDISEASECTDANDRHEUMATISM7INFLAMMATORYINHIBITORSSUCHASNONSTEROIDALANTIINFLARMNATORYANALGESICANDSTEROIDALDRUGSWASUSED8WITHINCOMPLETEEASEHISTORYCORRELATIONBETWEENPLASMAASYMMETRICDIMETHYLARGININEANDDIFFERENTTYPESOFCORONARYHEARTDISEASECAOYUETAL3O312MAJORINSTRUMENTSANDREAGENTSHITACH17170SAUTOMATEDBIOCHEMISTRYANALYZERJAPANESEHITACHIACS180SEAUTOMATICELECTROCHEMICALIMMUNOANALYZERUSABAYERLC一10ADVPHIGHPERFORMANCELIQUIDCHROMATOGRAPHJAPANESESHIMADZUSEQUIOA512FULLDIGITALCOLORULTRASONICDIAGNOSTICAPPARATUSANDCAIMDIGITALSUBTRACTIONANGIOGRAPHYANGELSTARGERMANSIEMENSWATERSCHROMATOGRAPHICCOLUMNNOVAPAKC18SHANGHAISHENGXILNDUSTRYCO,LTDTOTALCHOLESTEROLTCANDTRIGLYCERCIDETGTESTINGREAGENTSICHUANMAKERBIOTECHNOLOGYCO,LTDHIGHDENSITYLIPOPROTEINHDLTESTINGREAGENTCHINESEWAKOPURECHEMICALINDUSTRIESLTDPLASMAVWFTESTKITSHANGHAISUNBIOMETRICTECHNOLOGIESCO,LTDPLASMANOTESTKITNANJINGJULYPHARMACEUTICALCO,LTD13SELECTIVECORONARYANGIOGRAPHYCORONARYANGIOGRAPHYWASCONDUCTEDBYRADIALALRTERYAPPROACHWITHPROJECTIONOFMULTIPLEBODYPOSITIONSTHEANGIOGRAPHYRESULTSWEREDRAWNBYQUANTITARIVEANALYSISONTHEBLOODVESSELSTENOSISLEVELOFLEFTMAINCORONARYARTERYLM,LEFTANTERIORDESCENDINGCORONARYARTERYLAD,LEFTCIRCUMFLEXARTERYLCXAND啦HTCORONARYARTERYRCABY2EXPERIENCEDDOCTORSWITHRESPECTIVEAPPLICATIONOFUNIVERSALOCULARESTIMATEMETHODOFVESSELDIAMETERINCASEOFTHEBLOODVESSELSTENOSISLEVELOFCORONARYARTERYWASMORETHAN50ITWASCLASSIFIEDINTOTHECHDGROUP14BLOODCOLLECTIONANDDETERMINATIONOFBIOCHEMICALPARAMETERS141SAMPLECOLLECTIONANDDETERMINATIONOFBLOODGLUCOSEANDLIPIDBEFOREACCEPTINGCORONARYANGIOGRAPHY,ALLPATIENTSKEPTHOLLOWSTOMACHFOR8HOURSWHOSERIGHTFEMORALARTERYORRADIALARTERYWASPUNCTUREDBYSELDINGERMETHODAFTERCONVENTIONALDISINFECTION,DRAPING,ANDLOCALANESTHESIAWITHPROCAINEORLIDOCAINE,ANDPUTINTOARTERYSHEATHTENMILLILITERARTERYBLOODSLOWLYDRAWEDOUTALONGTHEARTERYSHEATHANDTHENDIVIDEDINTO2PARTS,WHICHWASPLACEDINTOA10MLANTICOAGULANTHEPARINSOLUTIONPIPEANDAGENERALCENTRIFUGALPIPE,RESPECTIVELYAFTERCENTRIFUGATEDFOR15MINAT3000R/RAIN,SUPERNATANTPLASMAANDSEDLMRESPECTIVELYWEREPLACEDINTOEPPIPESIN一80C【REFRIGERATORINTHEMEANTIME,THEBIOCHEMICALINDICATORSINCLUDINGLIVERANDKIDNEYFUNCTIONS,BLOODUCOSEANDLIPIDWEREEXAMINEDINCLINICALLABORATORYDEPTOFTHIRDXIANGYAHOSPITA1142DETERMINATIONOFPLASMAADMATHECONTENTSOFADMAINTHEPLASMAWEREMEASUREDBYHIGHPERFORMANCELIQUIDCHROMATOGRAPHYHPLCBRIEFLY,HPLCWASCARRIEDOUTUSINGASHIMADZULC一6ALIQUIDCHROMATOGRAPHWITHSHIMADZUSCL6ASYSTEMCONTROLLERANDSHIMADZUSIC6AAUTOSAMPLEROPHTHALDIADEHYDEADDUCTSOFMETHYLATEDAMINOACIDSANDINTERNALSTANDARDADMAPRODUCEDBYPRECOLUNMMIXINGWEREMONITOREDUSINGAMODELRF530FLUORESCENCEDETECTORSETATKEX338ANDHEM425NMONARESOLVEC18COLUMNTHEPROTEINSINTHEPLASMAWEREREMOVEDUSING5SULFOSALICYLICACIDSAMPLESWEREELUTEDFROMTHECOLUMNUSINGALINEARGRADIENTCONTAININGMOBILEPHASEACOMPOSEDOF005MMOLPH68SODIUMACETATEMETHANOLTETRAHYDROFURANVOLUMERATIOWAS81181ANDMOBILEPHASEBCOMPOSEDOF005MMOLSODIUMACETATEMETHANOLTETRAHYDROFURANVOLUMERATIOWAS22771ATAFLOWRATEOF1ML/MIN143DETERMINATIONOFPLASMAVWFFACTORENZYMELINKEDIMMUNOSORBENTASSAYELISAWASAPPLIEDTODETERMINETHECONTENTOFPLASMAVWFTHEDETAILEDOPERATIONSWERECARRIEDOUTINACCORDANCEWITHDIRECTIONSOFTHETESTKIT,ANDVALUESWEREREADAT492NMBYMICROPLATEREADERASTANDARDCURVEWASPLOTTEDATPLASMACONTENTOFVWFCRITERIA,ANDTHEVWFCONTENTOFSAMPLEWASTRACKEDDOWNFROMTHESTANDARDCURVE144DETERMINATIONOFNOINPLASMATHELEVELOFNOINPLASMA,REFLECTEDINDIRECTLYBYTHECONTENTOFNITRITEANDNITRATE,WASMEASUREDBRIEFLY,NITRATEWASCONVERTEDTONITRITEWITHNITRITE中南大学医学版,2010,354HTTP/XBYXXYSMNETREDUCTASE,ANDTHETOTALNITRITEWASMEASUREDWITHTHEGRIESSREAGENTTHEABSORBANCEWASDETERMINEDAT540NMWITHASPECTROPHOTOMETER15STATISTICALANALYSISTHEMEASUREMENTDATAWEREPRESENTEDASMEANSTANDARDDEVIATIONSALLSTATISTICALANALYSISWASCARRIEDOUTBYSPSSSOFTWAREVERSION110FORWINDOWS,SPSSINC,CHICAGO,ILLINOIS,USATHEENUMERATIONDATAWEREASSESSEDWITHXTESTTHEINDEPENDENTSAMPLESTTESTANDONEWAYANOVAWEREUSEDTOEVALUATETHESTATISTICALDIFFERENCESAMONGDIFFERENTGROUPSP005WASCONSIDEREDASSTATISTICA1D讯REBEE2RESULTS21BASICCHARACTERISTICSOFSUHJECTSTCANDTGINPLASMAHADNOOBVIOUSDIFFERENCEAMONGTHESAP,ACSANDNONCHDGROUPAGESOFTHESAPANDACSGROUPSWEREOLDERTHANTHATOFNONCHDGROUP,WHILEHDLINTHENONCHDGROUPWASSIGNIFICANTLYHIGHERTHANTHATINTHESAPANDTHEACSGROUPSMALE/FEMALERATIOINTHEACSGROUPRANKEDTHEHIGHEST,THATINTHESAPGROUPWENTSECOND,ANDTHATINNONCHDGROUPWASTHELOWESTTAB1TAB1COMPARISONBETWEENSAPACS,ANDNONCHDGROUPCOMPAREDWITHTHENONCHDGROUP,PO05COMPAREDWITHTHEACSGROUP,PO0522PLASMAADMALEVELWASINCREASEDINTHEACSGROUPTHEPLASMAOFADMALEVELOFTHEACSGROUPSIGNIFICANTLYINCREASEDCOMPAREDWITHTHENONCHDANDTHESAPGROUPSP005HOWEVER,THEPLASMAADMALEVELOFSAPGROUPTENDEDTOINCREASEBUTTHETRENDDIDNOTREACHSIGNIFICANCE,COMPAREDWITHTHENONCHDGROUPP005,TAB2TAB2COMPARISONINPLASMALEVELSOFADMA,NO,VWFAMONGSAP,ACS,ANDNONCHDGROUPCOMPAREDWITHNONCHDGROUP,P005COMPAREDWITHSAPGROUP,AP00523DECLINEOFPLASMANOLEVELSINTHESAPANDACSGROUPSCOMPAREDWITHTHENONCHDGROUP,THEPLASMANOLEVELINTHESAPANDACSGROUPSBOTHSIGNIFICANTLYDECREASEDANDTHEREDUCEDDEGREEOFPLASMANOLEVELINTHEACSGROUPWASMORETHANTHATINTHESAPGROUPP005,TAB224INCREASEDPLASMALEVELSOFVWFINSAPANDACSGROUPSCOMPAREDWITHTHENONCHDGROUP,THEPLASMACORRELATIONBETWEENPLASMAASYMMETRICDIMETHYLARGLNINEANDDIFFERENTTYPESOFCORONARYHEARTDISEASECAOYU,ETALVWFLEVELINTHECANTLYDECREASEDCANTDIFFERENCEINANDACSGROUPS3SAPANDACSGROUPSBOTHSIGNIFIP0051THEREWASNOSIGNIFIPLASMALEVELSOFVWFINTHESAPP005,TAB2DISCUSSIONASANEWMARKEROFCARDIOVASCULARDISEASE,THEFUNCTIONOFADMAINFACILITATINGATHEROSCLEROSISHASBEENRECOGNIZEDADMAISGENERATEDFROMHYDRO1YSISOFTHEPROTEINSINWHICHTHEARGININERESIDUESAREMETHYLATEDBYARGININEMETHYHRANSFERASEINVIVO,PARTOFADMAISCLEAREDBYRENALEXCRETIONWHEREASMOSTOFADMACLEARANCEISDEPENDENTONTHEENZYMEDIMETHYLARGININEDIMETHYLAMINOHYD【ROLASEDDAHADMACANCOMPETITIVELYINHIBITTHEACTIVITYOFNOSANDDECREASETHESVNTHESIS0FNOINADDITIONTOTHEEFFECTOFVASODILATION,NOALSOEXERTSTHEEFFECTONTHEINHIBITIONOFPLATELETAGGREGATION,CELLADHESION,SMOOTHMUSCLECELLSPROLIFERATION,ANDROSPRODUCTION,WHICHPLAYANIMPORTANCEROLEINMAINTAININGTHEINTEGRITYOFVASCULARENDOTHELIUMANDPREVENTATHEROSCLEROSISDEVELOPMENTTHEREAREMULTIPLEFACTORSTHATLEADTOTHEREDUCTIONOFNOAMONGTHEM,THEREDUCTIONINNOSACTIVITYISACFUCIALONESINCEADMACANCOMPETITIVELYINHIBITNOSACTIVITY,WEHYPOTHESIZEDTHATTHEINCREASEINADMALEVELMAYCONTRIBUTETOTHEREDUCTIONOFNOSACTIVITYTHEREISPLENTYOFEVIDENCETHATTHEPLASMALEVELOFADMAWASSIGNIFICANTLYINCREASEDINMANYCARDIOVASCULARDISEASESSUCHASHYPERTENSION,CORONARYHEARTDISEASE,HEARTFAILUREANDATHEROSCLEROSIS,SUPPORTINGTHECONCEPTTHATADMAISANOVELRISKFACTORFORCARDIOVASEU1ARDISEASES卜INGENERAL,CHDPATIENTSARECLASSIFIEDASSAPANDACSDEPENDINGONTHECLINICALSYMPTOMSTHEOCCURRENCEOFACSCLOSELYCORRELATESWITHINSTABILITYANDRAPTUREOFCORONARYPLAQUESASWELLASTHEFORMATIONOFSECONDARYTHROMBUSITHASBEENSHOWNTHATTHEPLASMALEVELSOFADMAINCHDPATIENTSSIGNIFICANTLYELEVATED,HOWEVER,MOSTOFSTUDIESWERENOTINVOLVEDINCLINICALCLASSIFICATIONOURSTUDYSHOWEDTHATTHEPLASMALEVELSOFADMAINTHEACSGROUPDRAMATICALLYELEVATEDCOMPAREDWITHTHENONCHDANDSAPGROUPSTHEADMALEVELSINTHESAPGROUPSHOWEDATENDENCYTOINCREASE,SUGGESTINGTHATTHECHANGEOFPLASMALEVELOFADMAMORECLOSELYCORRELATESTOTHEACSCAVUSOGLU,ETA1INDICATEDTHATTHEPLASMALEVELOFADMAHADDEFINITEVALUEONTHEPROGNOSISOFACSPATIENTSTHEREFORE,THEPLASMALEVELOFADMANOTONLYCORRELATESWITHTHEOCCURRENCEANDDEVELOPMENTOFCORONARYATHEROSCLEROSIS71,BUTALSOINDIRECTLYREFLECTSTHESTABILITYANDDEGREEOFTHECORONARYATHEROSCLEROSISANDACCORDINGLYHASACERTAINEVALUATIONVALUEONCLINICALCHDTYPESANDSEVERITYOFDIABETICMICROANGIOPATHYWEALSOFOUNDTHEPLASMALEVELOFNOINTHEACSGROUPWASSIGNIFICANTLYREDUCEDINAGREEMENTWITHTHEREDUCTIONOFADMAINTERESTINGLY,THEREWASNOSIGNIFICANTCHANGEINTHEPLASMALEVELOFADMAINTHESAPGROUP,BUTTHENOLEVELMARKEDLYDECREASEDTHESERESULTSSUGGESTTHATTHEREEXISTEDOTHERMECHANISMSBESIDESADMA,TOMODULATETHEACTIVITYOFNOSANDTHEGENERATIONOFNOINADDITION,THEPLASMALEVELOFVWFINTHESAPANDACSGROUPSELEVATEDCOMPAREDWITHTHATINTHENONCHDGROUP,BUTTHEREWASNOSIGNIFICANTDIFFERENCEBETWEENTHESAPANDACSGROUPSTHESERESULTSWERENOTINCONSISTENTWITHTHECHANGEOFADMALEVELBUTINAGREEMENTWITHTHECHANG