CAJ | 학술논문

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(10 mg/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-κB p65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-κB p65表达水平显著高于对照组( P<0．001),阿托伐他汀组磷酸化NF-κB p65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。
목적：탐토아탁벌타정항경총동맥죽양경화형성작용급기가능궤제。방법36지웅성재지단백E( apolipoprotein E, ApoE)기인고제( ApoE-/-)소서수궤분위대조조、모형조화아탁벌타정조。대조조사이보통사료주가수술,모형조화아탁벌타정조균급여고지음식병주우측경총동맥투관술,술후제5주개시분별여생리염수화아탁벌타정(10 mg/kg,1차/d)관위。술후제8주말경고동맥취혈진행생화검측,병취우측경총동맥진행조직병이학검사。실시형광정량취합매련반응(polymerase chain reaction, PCR)검측반괴내 NF-κB mRNA표체,단백질인적법검측린산화 NF-κB p65단백표체。결과모형조화아탁벌타정조혈지수평균현저고우대조조( P균<0．05),아탁벌타정조혈지수평저우모형조,단차이무통계학의의。조직병이학관찰현시,모형조가견명현반괴형성,반괴내가견배사핵심구화신생미혈관；아탁벌타정조혈관내막명현증후,단관벽가견교완정적내피세포。모형조화아탁벌타정조반괴부하균현저고우대조조(P균<0．001),이아탁벌타정조반괴부하현저소우모형조(P<0．001)。실시형광정량PCR검측현시,모형조화아탁벌타정조NF-κB mRNA표체수평균현저고우대조조( P균<0．001),아탁벌타정조 NF-κB mRNA표체수평현저저우모형조(P=0．022)。단백질인적분석현시,모형조린산화 NF-κB p65표체수평현저고우대조조( P<0．001),아탁벌타정조린산화NF-κB p65표체수평현저저우모형조(P<0．001)。결론아탁벌타정가통과하조핵인자-κB감경경총동맥죽양경화。
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 atorvastatin 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-κB mRNA in the plaques. Western blotting was used to detect phosphorylated NF-κB p65. Results The lipid levels in the model group and the atorvastatin group were significant higher than those in the control group (al 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 cel s in the vessel wal 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 (al 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 the atorvastatin group were significantly higher than that in the control group (al P<0. 001), and the expression level of NF-κB mRNA in the atorvastatin group was significant lower than that in the model group (P= 0. 022). Western blotting showed that the expression level of the phosphorylated NF-κB p65 was significantly higher than that of the control group (P<0. 001), and the expression level of the phosphorylated NF-κB p65 was significantly lower than that in the model group (P<0. 001). Conclusions Atorvastatin may reduce atherosclerosis in the common carotid artery in ApoE-/-) mice by down-regulating NF-κB.