慢性低氧肺动脉高压大鼠肺部PPARγ表达变化的意义.docx

慢性低氧肺动脉高压大鼠肺部PPARγ表达变化的意义

向光明;刘焰

【摘要】目的探讨过氧化物酶增殖物激活受体γ(PPARγ)在慢性低氧肺动脉高压(HPAH)大鼠模型肺部及血管中的变化及意义.方法雄性SD大鼠40只,随机分为正常(NC)组、1周低氧(HC-1w)组、2周低氧(HC-2w)组、3周低氧(HC-3w)组.NC组于常氧条件下饲养于通风动物笼中3周,其余低氧组动物在每日9:00—17:00(8h/d)放入一体化低氧舱(O2体积分数10%)中进行低氧处理,时间分别为1周、2周、3周.右心导管法检测平均肺动脉压(mPAP),右心室收缩期末压力(RVSP);解剖心脏计算右心室肥厚指数RV/(LV+S).HE染色观察各组肺部中小动脉的形态学改变,计算血管壁厚百分比(WT%),Westernblot方法检测肺组织中PPARγ蛋白表达水平.结果HC各组大鼠mPAP、RVSP、RV/(LV+S)血流动力学指标均较NC组明显升高(P0.05).血管形态学显示HC各组相对于NC组,血管壁明显增厚,血管腔变狭窄,且随着时间延长,狭窄和增厚的程度加深.PPARγ在HC各组的表达与NC组相比均呈明显下降趋势,且随着时间延长,下降趋势更加明显.结论PPARγ对慢性低氧肺动脉高压的发生和发展有着重要的意义.%ObjectiveToinvestigatethesignificanceofperoxisomeproliferator-activatedreceptor(PPAR)γexpressioninthelungtissueofratswithchronichypoxicpulmonaryhypertension(HPAH).MethodsFortymaleSprague-Dawleyratswererandomlydividedintofourgroups(n=10foreachgroup):normalcontrolgroup(NC),hypoxiacontrolgroup-one-week(HC-1w),hypoxiacontrolgroup-two-week(HC-2w)andhypoxiacontrolgroup-three-week(HC-3w).Normalcontrolgroupwasraisedundernormaloxygenconditioninventilatedanimalcageforthreeweeks.TheotherHCgroupswereplacedinalowoxygenchamber(O2concentrationof10%)from9:00AM-5:00PM(8h/d)everydaybyoneweek,twoweeksandthreeweeks.Themeanpulmonaryarterialpressure(mPAP),rightventricularsystolicpressure(RVSP)weredetected.TheindexofrightventricularhypertrophyRV/(LV+S)wasmeasuredbydissectingratheart.Themorphologicalchangesofthesmallpul-monaryarterieswereobservedbyHEstaining,andthepercentageofvascularwallthickness(WT%)wascalculated.Theex-pressionlevelofPPARγproteinwasdetectedbyWestrenblotassay.ResultsThemPAP,RVSPandRV/(LV+S)weresig-nificantlyhigherinHCgroupsthanthoseofNCgroup(P0.05).ThemorphologyofpulmonaryarteriesshowedvesselwallthickeningandvesselluminastenosisinHCgroupscomparedwiththatofNCgroup.ThePPARγexpressioninlungtissuewassignificantlylowerinHCgr