Development of nano t-PA gene coating stent and its preventive effect on dog coronary artery stent thrombosis

(整期优先)网络出版时间:2017-03-13
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BackgroundTheregulationoft-PAgeneistheessenceandcoreofthrombosis.Therefore,thepresentstudyaimedtopreparenanot-PAgenecoatedstentandtoobserveitseffectoncoronarystentthrombosisindogs.MethodsHighlyexpressedt-PAgeneplasmidwasconstructedandalbuminnanot-PAgenecoatingstentwasprepared.Themajorbranchvesselsofdogcoronaryarterywerepre-expandedwitha3.0mm×20balloonwith8-10atmosphericpressure.10dogsofthecontrolgroupwereimplantedwithbaremetalstent;while12dogsoftheexperimentalgroupwereimplantedwithnanot-PAgenecoatingstent.Bothgroupswerenotgivenanti-coagulationtreatments.Bloodsamplesweretakenfort-PAandD-dimerbeforetheoperation,at1,2,4and8weeksafteroperation.Pathologicalanalysisfoundthrombosisinthecavityandthehyperplasiaoftheintima.t-PAexpressionwasdetectedbyimmunohistochemicalindirectly,andthethicknessoftheintimaofthesectioncrosswasdirectlymeasuredbymorphometry.Liver,heart,kidneysandlungweretakenforpathologicalobservation.ResultsAllexperimentalanimalssurvivedatpostoperative8weeks.Vascularstentthrombosiswasseenin10casesofthecontrolgroupwiththethrombosisrateof100%;whilewasseenin2casesamong12casesoftheexperimentalgroupwiththethrombosisratewas16.67%(P=0.00087).Immunohistochemicalstainingshowedthatthepositivet-PAgenetransfectionoftheexperimentalgroupwasmainlydistributedonthesurfaceofhyperplasiaintima,andvascularwallt-PAexpressionofthecontrolgroupwasnegative.Positivet-PAsignalwasnotfoundintheliver,heart,kidneysandlung.ConclusionNanot-PAgenevectorcoatingstentcaneffectivelyexpresst-PAinvascularwallandeffectivelypreventsstentthrombosis.