[文章编号]100723949(2003)1120520465205·方法学研究·三种大鼠动脉粥样硬化模型复制方法的比较郭延松,吴宗贵,杨军柯,黄高忠(第二军医大学长征医院心血管内科,上海200003)[关键词]病理学与病理生理学;大鼠动脉粥样硬化模型的复制;高脂+维生素D+内皮损伤;动脉粥样硬化,大鼠模型;高脂;维生素D;内皮损伤[摘要]为研究动脉粥样硬化的发病机制,比较了三种大鼠动脉粥样硬化斑块模型建立的方法。分别予单纯高脂、高脂+维生素D、高脂+维生素D+内皮损伤三种不同方法处理大鼠,90天后比较血脂、血钙、胸主动脉的形态学改变、巨噬细胞和α2平滑肌肌动蛋白含量。结果发现,三组实验组与正常对照组相比,总胆固醇、甘油三酯和低密度脂蛋白胆固醇均明显升高(P<0.01);高脂+维生素D组、高脂+维生素D+内皮损伤组与正常对照组和高脂组相比,血钙均明显升高(P<0.01);高脂+维生素D组、高脂+维生素D+内皮损伤与正常对照组相比,内膜增厚、中膜萎缩(P<0.05或P<0.01);单纯高脂组、高脂+维生素D组CD68为弱阳性,高脂+维生素D+内皮损伤组为强阳性;高脂+维生素D组内膜有较厚的α2平滑肌肌动蛋白阳性,高脂+维生素D+内皮损伤组斑块表面只有很薄的α2平滑肌肌动蛋白阳性;单纯高脂组只可形成高脂血症,无法形成动脉粥样硬化病变;高脂+维生素D组可形成纤维斑块;高脂+维生素D+内皮损伤组可形成较成熟的动脉粥样硬化斑块。证明了大鼠可作为研究动脉粥样硬化的良好动物模型,高脂+维生素D+内皮损伤组可形成较成熟的动脉粥样硬化斑块。[中图分类号]R363[文献标识码]AComparisonontheThreeDuplicationMethodsofAtherosclerosisModelinRatsGUOYan2Song,WUZong2Gui,YANGJun2Ke,andHUANGGao2Zhong(DepartmentofCardiovasology,ChangzhengHospital,SecondMilitaryMedicalUniversity,Shanghai200003)[KEYWORDS]Atherosclerosis;Rat;Model;Highlipid;VitaminD;EndotheliumInjure[ABSTRACT]AimToinvestigatepathogenesisofatherosclerosis,threemethodsforestablishmentofratanimalmodelwerecompared.MethodsThreedifferentmethods,includinghighlipidonly,highlipid+VitaminDoverload,andhighlipid+VitaminDoverload+endotheliuminjure,wereusedforinducingatherosclerosisinrats.After90days,serumlipid,serumcal2cium,morphologychangeofthoracicaortaweredetermined,andimmunohistochemicalassayofmacrophageand(2smoothmuscleactinwereperformed.ResultsThelevelsofserumtotalcholesterol(TC),triglyceride(TG),LDLCinthreegroups(hyper2lipidemiagroup,hyperlipidemia+vitaminD3group,andhyperlipidemia+vitaminD3+endotheliumdenudategroup)wereob2viouslyhigherthanthoseincontrolgroup(P<0.01).Thelevelsofserumcalciumintwogroups(hyperlipidemia+vitaminD3groupandhyperlipidemia+vitaminD3+endotheliumdenudategroup)werealsoobviouslyhigherthanthoseincontrolgroupandhyperlipidemiagroup(P<0.01).Comparedwithcontrolgroup,therewerethickerintima,thinnermediainhyperlipidemia+vitaminD3groupandhyperlipidemia+vitaminD3+endotheliumdenudategroup(P<0.05andP<0.01).Byimmunohis2tochemistry,theCD68positivelevelwerelowinhyperlipidemiagroupandhyperlipidemia+vitaminD3group,andhighinhyper2lipidemia+vitaminD3+endotheliumdenudategroup.Theα2actinpositivelevelinintimaisthickinhyperlipidemia+vita2minD3group,thininhyperlipidemia+vitaminD3+endotheliumdenudategroup.TheratstreatedwithhighlipidonlyshowedhyperlipidemiawithoutAslesion;theratstreatedwithhighlipid+VitaminDoverloadshowedfibrousplaque;thetypicalmatureatheromatousplaqueswerepresentedintheratstreatedwithhighlipid+VitaminDoverload+endotheliuminjurecreatesmatureatheromatousplaque.ConclusionsRatcanbeusedasaidealmodelforresearchatherosclerosis.Thematureatheromatousplaquemaycreatedbyhighlipid+VitaminDoverloadandendotheliuminjure.[收稿日期]2003201221[修回日期]2003206230[基金项目]国家重点基础研究发展规划...
