阿托伐他汀通过下调核因子-κB减轻载脂蛋白E基因缺陷小鼠颈总动脉粥样硬化  

Atorvastafin attenuates atherosclerosis of common carotid artery in apolipoprotein E genedeficient mice by down-regulating NF-κB

出　　处：《国际脑血管病杂志》2015年第8期611-616,共6页International Journal of Cerebrovascular Diseases

摘　　要：目的探讨阿托伐他汀抗颈总动脉粥样硬化形成作用及其可能机制。方法36只雄性载脂蛋白E（apolipoprotein E，ApoE）基因敲除（ApoE^-/-）小鼠随机分为对照组、模型组和阿托伐他汀组。对照组饲以普通饲料做假手术，模型组和阿托伐他汀组均给予高脂饮食并做右侧颈总动脉套管术，术后第5周开始分别予生理盐水和阿托伐他汀（10mg／kg，1次／d）灌胃。术后第8周末经股动脉取血进行生化检测，并取右侧颈总动脉进行组织病理学检查。实时荧光定量聚合酶链反应（polymerase chain reaction，PCR）检测斑块内NF—κB mRNA表达，蛋白质印迹法检测磷酸化NF-κBp65蛋白表达。结果模型组和阿托伐他汀组血脂水平均显著高于对照组（P均〈0．05），阿托伐他汀组血脂水平低于模型组，但差异无统计学意义。组织病理学观察显示，模型组可见明显斑块形成，斑块内可见坏死核心区和新生微血管；阿托伐他汀组血管内膜明显增厚，但管壁可见较完整的内皮细胞。模型组和阿托伐他汀组斑块负荷均显著高于对照组（P均〈0．001），而阿托伐他汀组斑块负荷显著小于模型组（P〈0．001）。实时荧光定量PCR检测显示，模型组和阿托伐他汀组NF—κB mRNA表达水平均显著高于对照组（P均〈0．001），阿托伐他汀组NF—κB mRNA表达水平显著低于模型组（P=0．022）。蛋白质印迹分析显示，模型组磷酸化NF—κBp65表达水平显著高于对照组（P〈0．001），阿托伐他汀组磷酸化NF-κBp65表达水平显著低于模型组（P〈0．001）。结论阿托伐他汀可通过下调核因子-κB减轻颈总动脉粥样硬化。Objective To investigate the effect of atorvastatin on atherosclerosis formation of common carotid artery and its possible mechanism. Methods A total of 36 male apolipoprotein E gene knockout （ApoE^-/-） mice were randomly divided into 3 groups： a control group, a model group, and an atorvastatin group. The mice of the control group were fed with normal diet and received a sham operation, while the mice in the model group and the atoi＇vastatin group were given high fat diet and received a right common carotid artery cannulation. At 5 weeks after procedure, the mice in the model group and the atorvastatin group were intragastric administration of normal saline and atorvastatin （10 mg/kg daily）, respectively. At 8 weeks after procedure, the blood from femoral arteries was obtained for biochemical detection, then right common carotid arteries were taken out for histopathological study. Real-time quantitative polymerase chain reaction （PCR） was used to detect the expression levels of NF-KB mRNA in the plaques. Western blotting was used to detect phosphorylated NF-KB p65. Results The lipid levels in the model group and the atorvastatin group were significant higher than those in the control group （all P 〈0. 05）. The lipid level in the atorvastatin group was lower than that in the model group, but there was no significant difference （P〉 0.05）. The histopathological study showed that the obvious plaque formation and the necrotic core and neovessels in plaques were observed in the model group; obviously thickened intima and more intact endothelial cells in the vessel wall were observed in the atorvastatin group. The plaque burden in the model group and the atorvastatin group was significantly higher than that in the control group （all P 〈 0. 001）, while the plaque burden in the atorvastatin group was significantly less than that in the model group （P 〈0. 001）. Real-time fluorescence quantitative PCR detection showed that the expression levels of NF-κB mRNA in the model group and th

关 键 词：动脉粥样硬化 颈总动脉 羟甲基戊二酰基COA还原酶抑制剂 NF-κB 炎症 载脂蛋白E类 疾病模型 动物 小鼠 阿托伐他汀 

分 类 号：R543.4[医药卫生—心血管疾病]