天普洛安劑量及安全性探討-2003

危重癥患者烏司他丁臨床應(yīng)用劑量探討天普洛安?（烏司他?。﹦┝考鞍踩蕴接憙?nèi)容提要體內(nèi)烏司他丁與疾病或炎癥反應(yīng)的關(guān)系天普洛安?（烏司他?。┑牧啃шP(guān)系天普洛安?（烏司他?。┑陌踩訩en-ichiroInoue.etal,J.Clin.Biochem.Nutr.,43,139–142,November2008炎癥反應(yīng)促進Bikunin和烏司他丁大量釋放，

從而抑制蛋白酶活性這是一項用烏司他丁天然缺失（-/-）與正常表達兩種基因型小鼠所進行的對比性研究。分別在這兩種基因型的小鼠腹腔內(nèi)注射1mg/kg內(nèi)毒素以誘導(dǎo)全身炎癥反應(yīng)。然后對比這兩種動物血液學(xué)和組織學(xué)的變化。KEN-ICHIROINOUE，etal:ProtectiveRoleofUrinaryTrypsinInhibitorinAcuteLungInjuryInducedbyLipopolysaccharide,ExpBiolMed230:281–287,2005Ken-IchiroInoue,etal:UrinaryTrypsinInhibitorProtectsagainstSystemicInflammationInducedbyLipopolysaccharide,MolPharmacol67:673–680,2005機體內(nèi)缺失烏司他丁會……?Closedsymbols:UTI(-/-)miceOpensymbols:WTmiceAnimalswereharvested72hafteri.p.injectionofvehicleorLPS*P＜

0.05versusvehicle-treatedmice**P＜

0.01versusvehicle-treatedmice#P＜

0.05versusLPS-treatedWTmice##P＜

0.01versusLPS-treatedWTmicelung

vehicleLPSvehicleLPSkidney

vehicleLPSvehicleLPSlivervehicleLPSvehicleLPS在烏司他丁缺陷動物，大量白細胞被羈押在各器官kidneyliverlung烏司他丁缺陷動物，各器官細胞損傷明顯加重UTInull(-/-)miceinjectedwithLPS;WTmiceinjectedwithLPS(C)UTInull(-/-)miceinjectedwithvehicle;(D)WTmiceinjectedwithvehicleKen-IchiroInoue,etal:UrinaryTrypsinInhibitorProtectsagainstSystemicInflammationInducedbyLipopolysaccharide,MolPharmacol67:673–680,2005天普洛安前體濃度與疾病嚴重程度及死亡率相關(guān)TheJournalofInfectiousDiseases2003,188:919–26病情越嚴重，血漿和尿液中烏司他丁水平越低SHIDELIN,etal.JournalofGastroenterologyandHepatology(2004)19,327–332Child-PushC級患者的血漿和尿液UTI水平顯著低于A級和B級患者肝硬化患者肝細胞癌患者*P<0.05;**P<0.01嚴重疾病患者烏司他丁水平不足以消除被激活的酶Insufficientproductionofurinarytrypsininhibitorforneutrophilelastasereleaseaftercardiacarrest.SHOCK2008,29(5):549-552Controlgroup:8位健康志愿者Shortcardiacarrest:11位心臟驟停后30分鐘內(nèi)復(fù)蘇患者Longcardiacarrest:25位心臟驟停后超過30分鐘復(fù)蘇患者NE:粒細胞彈性蛋白酶ARDS患者肺泡中烏司他丁濃度不足以滅活PMNEARDSgroup(n=8)Controlgroup(n=8)Inconclusion,PMNEactivityintheBALFofpost-surgericalARDSisnotinhibitedbythesmallamountofUTIthatispresentintheBALFSurgToday,JpnJSurg(1999)29:1030-33烏司他丁是保護機體免受炎性損害的重要機制當疾病進展到一定程度，體內(nèi)烏司他丁水平嚴重不足小結(jié)烏司他丁抑制炎癥的效果與其濃度有密切依賴關(guān)系HumanmonocyteswerepreincubatedwithUTI(1,000U/ml)for30minandthenstimulatedwithLPS(100ng/ml).〇

control;□UTIwithoutLPS;●LPS;■,LPS+UTI.*P0.01vs.control;?P0.01vs.LPS.HumanmonocyteswerepreincubatedwithvariousconcentrationsofUTIfor30minandthenstimulatedwithLPS(100ng/ml).Fourhoursafterstimulation,PerenleiMolor-Erdene,etal.

AmJPhysiolHeartCircPhysiol288:H1265–H1271,2005.高濃度的烏司他丁對溶酶體膜穩(wěn)定作用更明顯Effectsofulinastatin(UT;U/ml)onN-acetyl-b-D-glucosaminidase(NAG)releasefromL2cellsaftertreatmentwith2uMantimycinA(A2).*P<0.05vs.A2;**P<0.05vs.control.PulmonaryPharmacology&Therapeutics(1999)12,1–6天普洛安對LPS肺損傷的保護作用具有劑量相關(guān)性EffectsofUTIonLPS-inducedchangesintheconcentrationofinterleukin-8inbronchoalveolarlavagefluid(BALF)andwet/dryweight(W/D)ratio.BALFandlunglobewerecollected6hafterthestartofthesalineorLPSinfusion.Eachvaluerepresentsmean±SDfromsevenrabbits.*P<0.05versusgroupSaline-Only,?P<0.05vs.groupLPS-Only,?P<0.01vs.groupLPS-Only.EffectsofUrinaryTrypsinInhibitoronLipopolysaccharide-InducedAcuteLungInjuryinRabbitsInflammation2011EffectsofUTIonlungtissuedamageinrabbitsat6hafterthestartofsalineorLPSinfusion.RepresentativehotomicrographiesshowinghematoxylinandeosinstainingsampleswithmedianvaluesinagroupSaline-Only,bgroupLPS-Only,andcgrouppre-UTI-High.Originalprintmagnifications×200.Lunginjuryscored:lunginjurywasscoredfrom0(nodamage)to4+(severedamage)accordingto