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1、乌司他丁对全肝缺血再灌注肺损伤的保护作用及机制赵东1,杨拔贤1,闫征2,姜春玲1,贾若1(1.北京大学人民医院麻醉科;2.北京大学人民医院中心实验室)摘要:目的:观察乌司他丁对大鼠全肝缺血再灌注肺损伤的保护作用及其机制探讨。方法:建立大鼠全肝缺血再灌注模型,24只SD大鼠随机分为假手术对照组(C组),全肝缺血30min、再灌注60min组(I组)和缺血前10min静脉注射乌司他丁+全肝缺血30min、再灌注60min组(U组)。检测支气管肺泡灌洗液(bronchoalveolarlavagefluid,BALF)中总蛋白含量、肺组织干/湿质量比(D/W)、肺组织髓过氧化物酶(myel
2、operoxidase,MPO)及超氧化物歧化酶(superoxidedismutase,SOD)含量,并以RT-PCR方法比较三组大鼠肺组织基质金属蛋白酶(matrixmetalloproteinase,MMP)14mRNA含量。结果:(1)与对照组比较,I组大鼠BALF总蛋白和MPO含量明显升高(P<0.05),乌司他丁可以显著抑制这种上升;(2)与对照组比较,I组和U组大鼠D/W和SOD显著降低(P<0.05),而乌司他丁则可以显著干预其降低程度;(3)与对照组比较,I组和U组大鼠肺组织MMP14mRNA含量显著增加(P<0.05),而乌司他丁则可以显著干预其升高程度。结论:大
3、鼠全肝缺血再灌注可产生严重的肺损伤,乌司他丁可以显著减轻肺损伤程度,可能的机制包括抑制肺组织MMP14mRNA的表达。关键词肺损伤;肝缺血再灌注损伤;乌司他丁;基因表达ProtectiveeffectandmechanismofulinastatinontotalhepaticischemiareperfusionassociatedlunginjuryinratsZHAODong,YANGBa-xian,YANZheng,JIANGChun-ling,JIAruo.1.DepartmentofAnesthesiology,PekingUniversityPeople’sHospit
4、al,Beijing,100044,China.2.LaboratoryofMolecularBiology,PekingUniversityPeople’sHospital,Beijing,100044,China.Abstract:Objective:Tostudytheroleofulinastatin-aproteaseinhibitorinprotectionoflungdamagefollowingtotalhepaticischemiareperfusioninrat.Methods:Twenty-fourhealthymaleSDratswererandomlydiv
5、idedintothreegroups(n=8ineachgroup).GroupCwasservedasshaminjurycontrol,groupIratsunderwent60minutesreperfusionafter30minutestotalhepaticischemiabyclampedthehepatichilumandUTI(ulinastatin,5x104U/kg)wasadministeredtoanimalsingroupU10minutesjustbeforetheocclusion.Theratsweresacrificedatendpointoft
6、heoperationandthelungtissuesweredividedintoseveralpartsfor(1)pathologicalsection;(2)pulmonaryMPOandSODactivity;(3)RT-PCRofMMP14mRNA.Inadditiontobronchoalveolarlavagefluidprotein(BALFP)content,andlungdrytowetweightratios(D/W)wererespectivelyexaminedineachgroup.Results:(1)ComparedtogroupC,content
7、ofMPOinlungtissuesandBALFPweremuchhigheringroupIandUTIcouldreversethistendencysignificantly(P<0.05);(2)lungD/WandpulmonarySODweremarkedlydecreasedduringhepaticischemiareperfusion,whilethemweresignificantlyincreasedinratspretreated