动脉粥样硬化易损斑块发生机制、检测方法与干预措施研究

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1、山东大学博士学位论文suspensionspreadstothewholecardiovascularsystemafterreleaseoftheaorticligation，whichmaycausesystemicadverseeffects．Therefore，thepresentstudywascarriedouttodevelopanewanimalmodelofvulnerableplaquesandinvestigatethepossiblemechanismsofexogenousp53-inducedplaqueinstabili

2、tyusingthisnewmodel．Objectives1．Toestabilishananimalmodelofvulnerableplaqueshistologicallyidenticaltohumans，easytodetect，andsuitabletoevaluatethetherapeuticeffectofmedicine．2．Toelucidatethepathologicalandmolecularmechanismsofexogenousp53-inducedplaqueinstability．MateriaIsandmet

3、hods1．AnimalprotocolAdultNewZealandWhitemalerabbits(n=40)underwentballoon-inducedendothelialinjuryintheabdominalaortaandthereafterwerefedahigh-cholesteroldiet(1％cholester01)for10weeks．Subsequently，theatherogenicdietwasreplacedbyaregulardietforanother6weeks．Thenrabbitswererandom

4、lydividedinto3groups：groupA(n=16)，groupB(n2l6)andgroupC(n=8)．RabbitsofgroupCwereeuthanizedforhistologicalandimmunohistochemicalstudiesattheendofweek16．Atweek16sincethebeginningoftheexperiment，theotherrabbitsunderwentintravascularultrasound(IVUS)studiesafteranesthesia．Afterthela

5、rgestplaqueintheabdominalaortawasimagedwithIVUS，amedianincisionintheabdomenwasmadeandthecorrespondingportionoftheabdominalaortawasisolated．UndertheguidanceofIVUS，a50．山suspensionofadenoviruscontainingp53(Sxl09pfu／m1)orlacZ(8x109pfu／m1)wasinjectedfromtheaorticadventitiaintothelar

6、gestplaqueintheabdominalaortaintheAd5-CMV．p53transfectedgrouporAd5-CMV．1acZtransfectedgroup，respectively．Toobservetheefficiencyoftransfection，3rabbitsineachgroupWereeuthanized．AccordingtoConstantinides’method，twoweeksafter7山东大学博士学位论文transfection，plaquedisruptionwastriggeredbyad

7、ministrationofChineseRussell’Svipervenom(o．15mg／kg，intraperitoneally)，followed30rainlaterbyhistamine(0．02mg／kgintravenously)at24hand48hbeforeeuthanization．2．BiochemicalstudiesBloodwasdrawnfromrabbitsfastingovernighttomeasurelipidprofileatthebeginningofthestudy,theendofweek10ont

8、erminationofhighcholesteroldietandtheendofweek16before