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目的 探讨载脂蛋白(Apo)CⅢ对动脉粥样硬化的影响及可能机制.方法 ApoCⅢ转基因小鼠与动脉粥样硬化易感的LDLR小鼠进行杂交,获得双基因修饰的模型小鼠为实验组;LDLR小鼠为对照组;两组均给予普通饮料喂养1个月后高脂喂养3个月.检测血浆总胆固醇(TC)、三酰甘油(TG)、脂质过氧化物8-异前列腺素、丙二醛(MDA)、还原性谷胱甘肽水平;对小鼠全主动脉和主动脉窦行油红O染色,平滑肌细胞特异性抗体SM22a染色和巨噬细胞特异性抗体MAC3染色,观察主动脉和流出道形态学改变;主动脉壁行活性氧(ROS)荧光探针-二氢乙啶染色,检测ROS含量水平;RT-PCR和Western印迹分别检测参与氧化应激和内质网应激相关基因的mRNA和蛋白表达水平.结果 高脂喂养3个月后,实验组TG水平显著高于对照组(P<0.01);实验组粥样硬化斑块面积明显大于对照组(P<0.05);实验组平滑肌细胞和巨噬细胞中硬化斑块面积均明显大于对照组(P<0.05).实验组8-前列腺素、MDA、ROS水平明显高于对照组,还原性谷胱甘肽水平明显低于对照组(P<0.05).实验组氧化应激相关基因纤溶酶原激活物抑制物(PAI)-1、还原型辅酶Ⅱ氧化酶(NOX)、内皮型一氧化氮合酶(eNOS)、超氧化物歧化酶(SOD)、p67 mRNA相对表达量显著高于对照组,内质网应激相关基因葡萄糖调节蛋白(GRP)78、X盒结合蛋白(XBP)-1、增强子结合蛋白同源蛋白(CHOP)相对表达量显著高于对照组(P<0.05);实验组氧化应激相关基因NOX-4蛋白和内质网应激相关基因GRP78蛋白的相对表达量均显著高于对照组(P<0.05).结论 ApoCⅢ可促进动脉粥样硬化形成,其机制与整体氧化应激水平升高及动脉壁氧化应激和内质网应激水平增加有关.“,”Objective To investigate the effect of apolipoprotein C Ⅲ (ApoCⅢ) on arterial atherosclerosis.Methods ApoCⅢtransgenic mice and hybridization with atherosclerotic susceptible LDLR mice were constructed to obtain double gene modified mouse model as experimental group;LDLR mice as the control group;all the mice were given high fat diet for 3 months. The levels of plasma total choles-terol,triglyceride,lipid peroxides 8-isoprostaglandin,malondialdehyde,reduced glutathione were tested. The morphological changes of aorta and outflow tract were observed. The mRNA and protein expression levels of stress-related genes in oxidative stress and endoplasmic reticu-lum were detected by RT-PCR and Western bold.Results After high fat diet 3 months,the level of triglyceride in experimental group was significantly higher than that in control group (P<0.01). The area of atherosclerotic plaque in experimental group was significantly higher than that in control group(P<0.05). The areas of sclerotic plaque in smooth muscle cells and macrophages of experimental group were sig-nificantly higher than those of control group(P<0.05). The levels of 8-prostaglandin,malondialdehyde and ROS in experimental group were significantly higher than those in control group,and the level of reductive glutathione was significantly lower than that of control group (P<0.05). The relative expression of PAI-1,NOX,eNOS,SOD and p67 mRNA in experimental group were higher than those in control group. The relative expression of GRP78,XBP-1 and CHOP in the endoplasmic reticulum were higher than those in control group(P<0.05). The relative expression of oxidative stress-related gene NOX-4 protein and endoplasmic reticulum stress-related gene GRP78 protein in experimen-tal group were significantly higher than those in control group(P<0.05).Conclusions ApoCⅢcould promote the formation of atherosclero-sis,and its mechanism is related to the increasing of total oxidative stress and the increasing of oxidative stress and endoplasmic reticulum stress.