建立基因敲除小鼠颈动脉粥样硬化模型课件

LipoproteinLipase(LPL)DeficiencyIncreasesPlasmaLipidLevelandEnhancesNeointimaFormationAfterCarotidArteryInjuryinapoEKnock-outMice

Candidategenesinlipoproteinmetabolism

LusisetalCirculation.2004LipoproteinLipaseintheArterialWall

PentikäinenetalArterioscler

Thromb

VascBiol.2002LipoproteinLipaseintheArterialWallPentikäinenetalArterioscler

Thromb

VascBiol.2002HypothesisLPLArterialresponsetoinjuryhyperlipidemicconditions？A1x2-mmstripoffilterpapersaturatedwith10%FeCl3solutionwasappliedtotheadventitialsurfaceofthesurgicallyexposedcarotidarteryfor3.0minutes,thenremoved.Thesurgicalincisionwassuturedwith4–0monofilament,andtheanimalwasreturnedtoitscage.CommoncarotidarteriesofapoE-/-,LPL+/-(ELK)mice(A)andapoE-/-,LPL+/+(EK)mice(B)8weeksafterferricchlorideinjuryneointimaformationaftercarotidarteryinjurybyFeCl3for

8weeksELKcarotidarterystainedwithH&EEKnoninjuredinjuredneointimaformationaftercarotidarteryinjurybyFeCl3for

8weekscarotidarterystainedwithH&EELKEKnoninjuredinjuredMeanIntimalandMedialCross-sectionalAreasofEKandELKMice8WeeksafterInjuryEKELK***EKELKmedia2.95x104±20005.98x104±1000intimal4.01x104±60008.15x104±2000lipiddepositaftercarotidarteryinjurybyFeCl3for

8weeksELKEKcontrolcarotidarterystainedwithOROnoninjuredinjuredlipiddepositaftercarotidarteryinjurybyFeCl3for

8weeksELKEKcarotidarterystainedwithOROnoninjuredinjuredlipiddepositaftercarotidarteryinjurybyFeCl3for

8weeksELKEKcarotidarterycounterstainedwithOROandhaematoxylininjurednoninjuredlipiddepositaftercarotidarteryinjurybyFeCl3for

8weeksELKEKcarotidarterycounterstainedwithOROandhaematoxylinnoninjuredinjuredMacrophagestainfor

8weeksELKEKELKEKVonWillebrandFactorStainfor

8weeks0week4weeks8weeksELK（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****NS0week4weeks8weeksELK(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**0week4weeks8weeksELK(n=4)118.3±7.9164.54±6.10109.7±4.46EK(n=3)85.19±17.7461.61±3.14109.53±2.90Pvalue0.190.680.980week4weeks8weeksELK17.75±0.7821.38±1.4521.75±2.18EK19.75±0.8822.63±0.7524.67±0.60Pvalue0.140.470.32NSNSNSEKELKneointimaformationaftercarotidarteryinjurybyFeCl3for

4weekscarotidarterystainedwithH&E

lipiddepositaftercarotidarteryinjurybyFeCl3for

4weeksELKEKcarotidarterycounterstainedwithOROandhaematoxylinReferenceMaryBethDeYoung,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,Katrin

Schäfer,Stavros

Konstantinides,MartinHalle,etalExerciseTrainingReducesNeointimalGrowthandStabiliz