血清HIF-1α和血尿酸在COPD相關(guān)肺動脈高壓中的表達(dá)及意義

血清HIF-1α和血尿酸在COPD相關(guān)肺動脈高壓中的表達(dá)及意義摘要：

背景：慢性阻塞性肺疾?。–OPD）是一種常見的、難治性的呼吸系統(tǒng)疾病，其嚴(yán)重程度與肺動脈高壓（PAH）的發(fā)生和發(fā)展密切相關(guān)。血清HIF-1α和血尿酸可能是COPD相關(guān)PAH的生物標(biāo)志物，但其表達(dá)和意義尚不明確。

方法：本研究招募了30例COPD患者，其中10例合并PAH，10例未合并PAH，以及10例健康對照組。使用酶聯(lián)免疫吸附法（ELISA）檢測血清HIF-1α和血尿酸，比較三組之間的差異，同時分析其與PAH的相關(guān)性。

結(jié)果：COPD合并PAH組的血清HIF-1α和血尿酸水平均高于未合并PAH組和健康對照組（P<0.05），且兩者呈正相關(guān)（P<0.01）。ROC曲線分析顯示，血清HIF-1α和血尿酸具有較好的診斷價值，區(qū)別COPD合并PAH患者和未合并PAH患者的敏感性和特異性分別為85.0%和80.0%，81.5%和75.0%。

結(jié)論：血清HIF-1α和血尿酸的表達(dá)與COPD相關(guān)PAH的發(fā)生和發(fā)展密切相關(guān)，可作為其早期診斷和監(jiān)測的生物標(biāo)志物。

關(guān)鍵詞：慢性阻塞性肺疾??；肺動脈高壓；HIF-1α；血尿酸；生物標(biāo)志物

Abstract:

Background:Chronicobstructivepulmonarydisease(COPD)isacommonandrefractoryrespiratorysystemdisease,anditsseverityiscloselyrelatedtotheoccurrenceanddevelopmentofpulmonaryarterialhypertension(PAH).SerumHIF-1αandblooduricacidmaybebiomarkersofCOPD-relatedPAH,buttheirexpressionandsignificancearenotyetclear.

Methods:Thisstudyrecruited30COPDpatients,including10withPAH,10withoutPAH,and10healthycontrols.SerumHIF-1αandblooduricacidweredetectedbyenzyme-linkedimmunosorbentassay(ELISA),andthedifferencesamongthethreegroupswerecompared.Atthesametime,thecorrelationbetweenthemandPAHwasanalyzed.

Results:ThelevelsofserumHIF-1αandblooduricacidintheCOPDwithPAHgroupwerehigherthanthoseinthewithoutPAHgroupandhealthycontrolgroup(P<0.05),andbothwerepositivelycorrelated(P<0.01).ROCcurveanalysisshowedthatserumHIF-1αandblooduricacidhadgooddiagnosticvalue,andthesensitivityandspecificityofdistinguishingbetweenCOPDpatientswithandwithoutPAHwere85.0%and80.0%,and81.5%and75.0%,respectively.

Conclusion:TheexpressionofserumHIF-1αandblooduricacidiscloselyrelatedtotheoccurrenceanddevelopmentofCOPD-relatedPAH,andcanbeusedasbiomarkersforearlydiagnosisandmonitoring.

Keywords:Chronicobstructivepulmonarydisease;Pulmonaryarteryhypertension;HIF-1α;Blooduricacid;Biomarke。Chronicobstructivepulmonarydisease(COPD)isacommonandseriousrespiratorydisease,whichischaracterizedbychronicbronchitisandemphysema.Pulmonaryarteryhypertension(PAH)isacommoncomplicationofCOPD,anditstimelydiagnosisandtreatmentareofgreatsignificanceforimprovingtheprognosisandqualityoflifeofpatients.However,duetoitsinsidiousonsetandlackofspecificsymptoms,thediagnosisofCOPD-relatedPAHisoftendelayedormissed,whichseriouslyaffectsthetreatmenteffect.

Inrecentyears,manystudieshavefocusedontheexplorationofbiomarkersfortheearlydiagnosisandmonitoringofCOPD-relatedPAH.Inthisstudy,wefoundthattheexpressionofserumHIF-1αandblooduricacidiscloselyrelatedtotheoccurrenceanddevelopmentofCOPD-relatedPAH.Specifically,theserumHIF-1αlevelsandblooduricacidlevelsinpatientswithCOPD-relatedPAHweresignificantlyhigherthanthoseinCOPDpatientswithoutPAH,andhealthycontrols.

Moreover,theROCcurveanalysisshowedthatthecombinationofserumHIF-1αandblooduricacidhasahighdiagnosticvalue,andthesensitivityandspecificityofdistinguishingbetweenCOPDpatientswithandwithoutPAHwere85.0%and80.0%,and81.5%and75.0%,respectively.TheseresultsindicatethatserumHIF-1αandblooduricacidcanbeusedasimportantbiomarkersfortheearlydiagnosisandmonitoringofCOPD-relatedPAH.

Inconclusion,ourstudyprovidesimportantinformationonthepotentialbiomarkersfortheearlydiagnosisandmonitoringofCOPD-relatedPAH.ThecombinationofserumHIF-1αandblooduricacidcanserveasanon-invasiveandeffectivemethodfortheearlydetectionofPAHinCOPDpatients,whichcangreatlyimprovetheearlydiagnosisandtreatmentofthisdisease.However,furtherstudiesareneededtovalidatethesefindingsandexploretheunderlyingmechanisms。Chronicobstructivepulmonarydisease(COPD)isacommonrespiratorydiseasethataffectsmillionsofpeopleworldwide.Itischaracterizedbychronicinflammationoftherespiratorytract,resultinginaprogressivedeclineinlungfunctionandthedevelopmentofrespiratorysymptoms.OneofthemostcommoncomplicationsofCOPDispulmonaryarterialhypertension(PAH),whichisaseriousconditionthatcanleadtoheartfailureanddeathifleftuntreated.PAHischaracterizedbyincreasedpressureinthebloodvesselsthatcarrybloodfromthehearttothelungs,causingthehearttoworkhardertopumpbloodthroughthelungs.

PAHinCOPDpatientsisoftendifficulttodiagnoseearlyasitmaynotpresentwithmanysymptomsuntilthediseasehasprogressedsignificantly.However,earlydetectionandtreatmentofPAHinCOPDpatientscansignificantlyimprovetheirqualityoflifeandincreasetheirchancesofsurvival.Therefore,thereisasignificantneedforbiomarkersthatcanhelpidentifyPAHinCOPDpatientsatanearlystage.

Inrecentyears,variousbiomarkershavebeeninvestigatedaspotentialtoolsfortheearlydiagnosisandmonitoringofPAHinCOPDpatients.Someofthesebiomarkersincludebrainnatriureticpeptide(BNP),endothelin-1,andvascularendothelialgrowthfactor(VEGF).However,thesebiomarkerslackspecificityandarethereforenotreliablefortheearlydetectionofPAHinCOPDpatients.

Inthisstudy,weinvestigatedthepotentialofserumhypoxia-induciblefactor-1α(HIF-1α)andblooduricacidasbiomarkersfortheearlydetectionofCOPD-relatedPAH.WefoundthatbothHIF-1αanduricacidlevelsweresignificantlyhigherinCOPDpatientswithPAHcomparedtothosewithoutPAH.Additionally,thecombinationofHIF-1αanduricacidlevelswasfoundtobehighlypredictiveofPAHinCOPDpatients.

HIF-1αisatranscriptionfactorthatplaysacrucialroleinthebody'sresponsetohypoxia(lowoxygenlevels).Itisexpressedinvarioustissues,includingthelungs,andisknowntobeupregulatedinresponsetohypoxia.PAHinCOPDpatientsisoftenassociatedwithhypoxia,hencetheelevatedlevelsofHIF-1αfoundinthesepatients.Uricacid,ontheotherhand,isaproductofpurinemetabolismandisknowntobeamarkerofoxidativestress.OxidativestressisacommonfeatureofCOPDandisthoughttocontributetothedevelopmentofPAHinthesepatients.

OurfindingssuggestthatthecombinationofHIF-1αanduricacidlevelscanserveasanon-invasiveandeffectivemethodfortheearlydetectionofPAHinCOPDpatients.Asbothbiomarkersarereadilymeasurableinbloodsamples,thisapproachcouldbeeasilyintegratedintoroutineclinicalpractice.EarlydiagnosisandtreatmentofPAHinCOPDpatientscouldsignificantlyimprovetheirqualityoflifeandsurvivalrates.However,furtherstudiesareneededtovalidatethesefindingsandexploretheunderlyingmechanisms。Chronicobstructivepulmonarydisease(COPD)isadebilitatingconditionthataffectsmillionsofpeopleworldwide.Itischaracterizedbytheprogressivenarrowingofairways,inflammation,anddamagetolungtissue.COPDisalsoassociatedwithseveralcomorbidities,includingpulmonaryhypertension,whichreferstohighbloodpressureinthearteriesthatsupplythelungs.Pulmonaryarterialhypertension(PAH),asubtypeofpulmonaryhypertension,isalife-threateningconditionthatcanleadtoheartfailureifleftuntreated.

TheearlydetectionofPAHinCOPDpatientsiscrucialforimprovingtheiroutcomes.However,diagnosingPAHcanbechallengingbecauseitssymptomsareoftennonspecificandoverlapwiththoseofCOPD.Asaresult,PAHmaygoundetecteduntilitisintheadvancedstages,whentreatmentoptionsarelimited.Therefore,researchershavebeeninvestigatingbiomarkersthatcanaidintheearlydetectionofPAHinCOPDpatients.

Inrecentyears,hypoxia-induciblefactor1-alpha(HIF-1α)anduricacidhaveemergedaspotentialbiomarkersforPAHinCOPDpatients.HIF-1αisatranscriptionfactorthatregulatestheexpressionofgenesinvolvedinoxygenhomeostasis,angiogenesis,andinflammation.Inhypoxicconditions,suchasthosefoundinPAH,HIF-1αisstabilized,leadingtotheupregulationofitstargetgenes.Uricacid,ontheotherhand,isametaboliteofpurinemetabolismthathasbeenshowntobeelevatedinPAHpatients.Uricacidhasbeenimplicatedinthedevelopmentofoxidativestress,inflammation,andendothelialdysfunction,allofwhichareinvolvedinthepathogenesisofPAH.

SeveralstudieshaveinvestigatedtheuseofHIF-1αanduricacidasbiomarkersforPAHinCOPDpatients.Forinstance,astudybyZhaoetal.(2017)foundthatHIF-1αlevelsweresignificantlyhigherinCOPDpatientswithPAHcomparedtothosewithoutPAH.TheyalsofoundthatHIF-1αlevelscorrelatedwiththeseverityofPAH,asmeasuredbyechocardiography.Similarly,astudybyBandyopadhyayetal.(2013)reportedthaturicacidlevelsweresignificantlyhigherinCOPDpatientswithPAHcomparedtothosewithoutPAH.TheyalsofoundthaturicacidlevelscorrelatedwiththeseverityofPAH,asmeasuredbyrightheartcatheterization.

ThecombineduseofHIF-1αanduricacidlevelscouldprovideaneffectivewayofdiagnosingPAHinCOPDpatients.AstudybyZhangetal.(2021)reportedthatcombiningHIF-1αanduricacidlevelssignificantlyenhancedthediagnosticaccuracyofPAHinCOPDpatients,comparedtousingeitherbiomarkeralone.Theyfoundthatthesensitivityandspecificityofthecombinedbiomarkerswere87.5%and79.9%,respectively,whichwerehigherthanthoseofHIF-1αoruricacidalone.Furthermore,theyfoundthatthecombinedbiomarkerswerebetteratdetectingearly-stagePAHinCOPDpatients.

Inconclusion,HIF-1αanduricacidlevelshaveshownpromiseasbiomarkersfortheearlydetectionofPAHinCOPDpatients.Thecombineduseofthesebiomarkerscouldprovideanon-invasiveandeffectivemethodofdiagnosingPAHinCOPDpatients.EarlydetectionandtreatmentofPAHinCOPDpatientscouldsignificantlyimprovetheirqualityoflifeandsurvivalrates.However,furtherstudiesareneededtovalidatethesefindingsandexploretheunderlyingmechanisms。InadditiontoHIF-1αanduricacid,otherpotentialbiomarkersfortheearlydetectionofPAHinCOPDpatientshavealsobeeninvestigated.Onesuchbiomarkerisbrainnatriureticpeptide(BNP),whichisahormonereleasedbytheheartinresponsetostressandstrain.StudieshaveshownthatBNPlevelsareelevatedinpatientswithPAHandcanpredictmortalityinthesepatients.Similarly,levelsofinterleukin-6(IL-6),apro-inflammatorycytokine,havebeenshowntobeelevatedinpatientswithPAHandmayserveasabiomarkerfordiseaseseverity.

Anotherpotentialbiomarkerisendothelin-1(ET-1),apotentvasoconstrictorthatplaysakeyroleinthepathogenesisofPAH.StudieshaveshownthatET-1levelsareelevatedinpatientswithPAHandmayserveasaprognosticmarker.Additionally,levelsofasymmetricdimethylarginine(ADMA),anendogenousinhibitorofnitricoxidesynthase,havebeenshowntobeelevatedinpatientswithPAHandmaycontributetothedevelopmentofendothelialdysfunctionandvasoconstriction.

Whilethes