血管平滑肌细胞中可溶性表氧化物水解酶在动脉粥样硬化疾病中的作用与其调节

《血管平滑肌细胞中可溶性表氧化物水解酶在动脉粥样硬化疾病中的作用与其调节》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。

1、-汕头大学医学院硕士学位论文VSMC中sEH表达增高，并且损伤3天后sEH的表达比损伤7天后的表达要高。sEH抑制剂均显著性减轻损伤后3天或7天动脉新生内膜的增厚和新生内膜与中膜面积比。对照组和单独TUPS组的中膜面积和外弹力纤维板的周长没有变化。综上所述，我们的研究发现，sEH在人冠状动脉粥样硬化VSMC中表达增高，在培养的VSMC中PDGF-BB增加sEH蛋白稳定性，sEH高表达促进VSMC的表型转化和迁移，sEH抑制剂可部分逆转由PDGF导致的VSMC的迁移。在大鼠颈动脉球囊拉伤模型中，损伤部位新生内膜的VSMC中sEH表达增高，sE

2、H抑制剂可减弱新生内膜的增厚。我们的研究提示sEH可能在AS病变的早期发挥重要作用，为AS的治疗提供了新的潜在靶点。【关键词】可溶性表氧化物水解酶；血管平滑肌细胞；表型转化；迁移；内膜增生---II---汕头大学医学院硕士学位论文AbstractThemigrationandproliferationofvascularsmoothmusclecells(VSMC)playanimportant roleinthedevelopmentofatherosclerosis(AS)andrestenosis.TheVSMCphenotypics

3、witching isprerequisiteforitsmigrationandproliferation.Epoxyeicosatrienoicacids(EETs),synthesized fromarachidonicacidbycytochromeP450epoxygenases,areconsideredas endothelium-derivedhyperpolarizingfactors,whichcaninduceVSMChyperpolarizationand vasorelaxation,aswellasdecreas

4、eadhesionmoleculeexpression.Solubleepoxidehydrolase (sEH)hydrolyzesEETstotheircorrespondingdihydroxyeicosatetraenoicacidsanddiminishes thebiologicalactivityofEETs.ItwasreportedthatsEHinhibitorsmarkedlyattenuatedthe angiotensinII-inducedhypertensionandcardiachypertrophy,and

5、suppressedtheprogressionof AS.However,theexpressionofsEHinhumanatheroscleroticlesionsindifferentstagesandthe underlyingmechanismhavenotbeenfullyelucidated.Ourpreviousresearchdemonstratedthat sEHwashighlyexpressioninearlystageofhumancoronaryatherosclerosis,suggestingitmay p

6、layaroleonthedevelopmentofAS.Theaimofthisstudyistoinvestigatetheexpressionof sEHinVSMCduringtheprogressionofASandtheunderlyingmechanisminvitroandinvivo, whichmayprovideapotientialnoveltherapeutictargetforAS.WefirstlytreatedratVSMCwithplatelet-derivedgrowthfactorBB(PDGF-BB)

7、andfound PDGF-BBupregulatedsEHatproteinlevelinadose-andtime-dependentlymanner,but PDGF-BBhadlittleeffectonsEHmRNAlevel.TransienttransfectionwithsEHpromoter constructandluciferaseactivityassaydemonstratedthatPDGF-BBtreatmentdidnotactivatethe sEHpromoter.Thisresultfurtherind

8、icatedPDGF-BBupregulatedsEHexpressionvia post-transcriptionallevel.Furtherexperimentsreve