建立基因敲除小鼠颈动脉粥样硬化模型英文

建立基因敲除小鼠颈动脉粥样硬化模型英文第1页/共27页Candidategenesinlipoproteinmetabolism

LusisetalCirculation.2004第2页/共27页LipoproteinLipaseintheArterialWall

PentikäinenetalArteriosclerThrombVascBiol.2002第3页/共27页LipoproteinLipaseintheArterialWallPentikäinenetalArteriosclerThrombVascBiol.2002第4页/共27页HypothesisLPLArterialresponsetoinjuryhyperlipidemicconditions？第5页/共27页A1x2-mmstripoffilterpapersaturatedwith10%FeCl3solutionwasappliedtotheadventitialsurfaceofthesurgicallyexposedcarotidarteryfor3.0minutes,thenremoved.Thesurgicalincisionwassuturedwith4–0monofilament,andtheanimalwasreturnedtoitscage.第6页/共27页CommoncarotidarteriesofapoE-/-,LPL+/-(ELK)mice(A)andapoE-/-,LPL+/+(EK)mice(B)8weeksafterferricchlorideinjury第7页/共27页neointimaformationaftercarotidarteryinjurybyFeCl3for

8weeksELKcarotidarterystainedwithH&EEKnoninjuredinjured第8页/共27页neointimaformationaftercarotidarteryinjurybyFeCl3for

8weekscarotidarterystainedwithH&EELKEKnoninjuredinjured第9页/共27页MeanIntimalandMedialCross-sectionalAreasofEKandELKMice8WeeksafterInjuryEKELK***EKELKmedia2.95x104±20005.98x104±1000intimal4.01x104±60008.15x104±2000第10页/共27页lipiddepositaftercarotidarteryinjurybyFeCl3for

8weeksELKEKcontrolcarotidarterystainedwithOROnoninjuredinjured第11页/共27页lipiddepositaftercarotidarteryinjurybyFeCl3for

8weeksELKEKcarotidarterystainedwithOROnoninjuredinjured第12页/共27页lipiddepositaftercarotidarteryinjurybyFeCl3for

8weeksELKEKcarotidarterycounterstainedwithOROandhaematoxylininjurednoninjured第13页/共27页lipiddepositaftercarotidarteryinjurybyFeCl3for

8weeksELKEKcarotidarterycounterstainedwithOROandhaematoxylinnoninjuredinjured第14页/共27页Macrophagestainfor

8weeksELKEK第15页/共27页ELKEKVonWillebrandFactorStainfor

8weeks第16页/共27页0week4weeks8weeksELK（n=4）61.52±11.09113.9±5.98270.17±24.29EK（n=3）53.96±18.1761.61±3.1485.07±9.40Pvalue0.760.00150.0016****NS第17页/共27页0week4weeks8weeksELK(n=4)395.5±34.89718.7±40.52939.32±46.67EK（n=3）239.6±59.77530.7±59.52686.08±56.66Pvalue0.0970.040.018NS**第18页/共27页0week4weeks8weeksELK(n=4)118.3±7.9164.54±6.10109.7±4.46EK(n=3)85.19±17.7461.61±3.14109.53±2.90Pvalue0.190.680.98第19页/共27页0week4weeks8weeksELK17.75±0.7821.38±1.4521.75±2.18EK19.75±0.8822.63±0.7524.67±0.60Pvalue0.140.470.32NSNSNS第20页/共27页EKELKneointimaformationaftercarotidarteryinjurybyFeCl3for

4weekscarotidarterystainedwithH&E

第21页/共27页lipiddepositaftercarotidarteryinjurybyFeCl3for

4weeksELKEKcarotidarterycounterstainedwithOROandhaematoxylin第22页/共27页第23页/共27页ReferenceMaryBethDeYoung,CliffordTom,DavidA.Dichek,etalPlasminogenActivatorInhibitorType1IncreasesNeointimaFormationinBalloon-InjuredRatCarotidArteries.Circulation.2001;104:1972-1977KoichiKaikita,AgnesB.Fogo,LijunMa,JohnA.Schoenhard,NancyJ.Brown,DouglasE.Vaughan,etalPlasminogenActivatorInhibitor-1DeficiencyPreventsHypertensionandVascularFibrosisinResponsetoLong-termNitricOxideSynthaseInhibition.Circulation.2001;104:839-844YanhongZhu,PeterM.Farrehi,WilliamP.Fay,etalPlasminogenActivatorInhibitorType1EnhancesNeointimaFormationAfterOxidativeVascularInjuryinAtherosclerosis-ProneMice.Circulation.2001;103:3105-3110MariannePynn,KatrinSchäfer,StavrosKonstantinides,MartinHalle,etalExerciseTrainingReducesNeointimalGrowthandStabilizesVascularLesionsDevelopingAfterInjuryinApolipopr