肺高压生化标记物

《肺高压生化标记物》由会员上传分享，免费在线阅读，更多相关内容在教育资源-天天文库。

1、张锐，荆志成心肺循环中心肺动脉高压生物标记物和预后BiomarkersinPulmonaryArterialHypertension生物标记物？评价临床疗效定义明确的临床终点事件临床终点事件替代指标6分钟步行距离生化标志物......*BiomarkersDefinitionsWorkingGroup.ClinPharmacolTher.2001;69:89-95.NIH*:可以被客观测量并且作为正常生物学过程、发病过程或者对于治疗干预的药理学反应指示某些疾病所致的病理状态下，血清中可测得的含量增高的化学物质。（体液、外周静脉血……）生物标记物？疾病诊断和

2、严重程度疗效判定疾病进展预后评估评价重要指标肺动脉高压候选生物标记物内皮功能障碍:ET-1、PGI2、NO神经体液过度激活:Catecholamines、Renin、Norepinephrine、Angiotensin血小板/凝血:Thromboxane、Serotonin、vWF、D-dimer,PAI-1ET-1andNerohormanalcorrelatewithsurvivalofPPHGalièN,etal.EurJClinInvest1996;26:141.481.00.50.00122436Survival(%)P=0.04—ET-1≥4.

3、3pg/ml----ET-1<4.3pg/mlmonthsBaseYear1Year2Year3Year4Year50.80.60.40.21.0EstimatedSurvival(%)norepinephrine<370ng/mlnorepinephrine=370to500ng/mlnorepinephrine>5000ng/mlNootensM.JACC1995;7:1581-1585.Nerohormonalactivationoccursinpatientswithisolatedrightventricularfailure.Theelevat

4、ioninendothelinlevelsisconsistentwithiterelaeaseinresponsetoPH.ESC/ERSGUIDELINESGalièN,etal.EurHeartJ2009;30(20):2493-2537.Brainnatriureticpeptide(BNP)/NT-proBNPWaewickG.EurRespirJ2008;32(2):503-512.Brainnatriureticpeptide(BNP)/NT-proBNPCOOHHPLGGPSSSAYTLRRAPPSSSSSSRRRCRCCCGGGKKKMM

5、DIFLLVVQHPSSSSSSRRRCRCCCGGGKKKMMDIFLLVVQHfurinHPLGGPSSSAYTLRRAPproBNPBNPCOOHNT-proBNPH2NCOOHH2NH2N7710810811107076SchematicofproBNPshowingenzymaticcleavageintobiologicallyactiveBNPandNT-proBNP.Brainnatriureticpeptide(BNP)/NT-proBNPBNPNT-proBNP成分32个氨基酸76个氨基酸生物活性有无来源proBNP裂解proBNP裂解

6、半衰期18min60-120min清除中性内肽酶受体清除、肾脏清除肾脏清除体外室温稳定性4h（采集后马上开始降解）>72h受年龄增长影响+++++可否床旁即时检测是否完成学术论文（篇）137039CHF诊断Cut-off值100pg/ml年龄<75:125pg/ml年龄≥75:450pg/mlBNP：判断右心功能不全血浆BNP浓度与肺动脉高压患者右心室功能不全的程度成比例增加2003001000PlasmaBNPLevels(pg/ml)**†Cont.RVVORVPO210PlasmaBNP/ANPRatio*†Cont.RVVORVPOChangein

7、BNPinsurvivorstreatedwithprostanoidsBNP：观察药物疗效NagayaN,etal.Circulation.2000;102:865-870.BaselineplasaminPPHaccordingtoNYNAclass.160012008004000PlasmaBNPLevel(pg/ml)Control(n=15)NYHAII(n=6)NYHAIII(n=42)NYHAIV(n=12)BNP*†‡*†*Time(months)Survivalrate(%)100806040200012243648BNP<150pg/m

8、LBNP≥150pg/mLBaselineBNPFollow-up