CAJ | 학술논문

目的探讨瑞舒伐他汀对载脂蛋白E基因敲除(apoE-/-)小鼠主动脉粥样硬化的影响.方法取apoE-/-小鼠18只建立动脉粥样硬化模型,C57BL/6小鼠12只为对照组.apoE-/-小鼠予高脂饲料,C57BL/6小鼠予普通饲料.12周后,随机抽取C57BL/6小鼠和apoE-/-小鼠各6只,判断是否成模.将成模后余下的12只apoE-/-小鼠随机分为模型组和瑞舒伐他汀治疗组(瑞舒伐他汀10 mg·kg-1·d-1灌胃),每组6只.余下的6只C57BL/6小鼠作为对照组.再过12周后处死小鼠,行血脂及主动脉HE、Masson、油红O染色观察动脉斑块,免疫组织化学方法检测主动脉组织平滑肌肌动蛋白(α-SMA)、转化生长因子β1(TGF-β1)、巨噬细胞表面分子-3(Mac-3)表达.结果模型组小鼠胆固醇、低密度脂蛋白水平均高于对照组(P均＜0.01),甘油三酯水平与对照组比较差异无统计学意义.模型组小鼠主动脉组织内可见明显动脉粥样硬化斑块形成,α-SMA、TGF-β1和Mac-3表达均较高于对照组(P均＜0.01).瑞舒伐他汀治疗组小鼠胆固醇、低密度脂蛋白、甘油三酯水平与模型组比较差异无统计学意义,但斑块内脂肪含量少于模型组,胶原含量多于模型组.治疗组α-SMA表达与模型组比较差异无统计学意义,治疗组TGF-β1、Mac-3表达均低于较模型组(P均＜0.01).结论瑞舒伐他汀可以减轻apoE-/-小鼠动脉粥样硬化模型中的脂质沉积和炎症反应,可以增加其胶原含量,利于斑块的稳定,具有抗动脉粥样硬化的作用,对血脂无影响.
목적 탐토서서벌타정대재지단백E기인고제(apoE-/-)소서주동맥죽양경화적영향.방법 취apoE-/-소서18지건립동맥죽양경화모형,C57BL/6소서12지위대조조.apoE-/-소서여고지사료,C57BL/6소서여보통사료.12주후,수궤추취C57BL/6소서화apoE-/-소서각6지,판단시부성모.장성모후여하적12지apoE-/-소서수궤분위모형조화서서벌타정치료조(서서벌타정10 mg·kg-1·d-1관위),매조6지.여하적6지C57BL/6소서작위대조조.재과12주후처사소서,행혈지급주동맥HE、Masson、유홍O염색관찰동맥반괴,면역조직화학방법검측주동맥조직평활기기동단백(α-SMA)、전화생장인자β1(TGF-β1)、거서세포표면분자-3(Mac-3)표체.결과 모형조소서담고순、저밀도지단백수평균고우대조조(P균＜0.01),감유삼지수평여대조조비교차이무통계학의의.모형조소서주동맥조직내가견명현동맥죽양경화반괴형성,α-SMA、TGF-β1화Mac-3표체균교고우대조조(P균＜0.01).서서벌타정치료조소서담고순、저밀도지단백、감유삼지수평여모형조비교차이무통계학의의,단반괴내지방함량소우모형조,효원함량다우모형조.치료조α-SMA표체여모형조비교차이무통계학의의,치료조TGF-β1、Mac-3표체균저우교모형조(P균＜0.01).결론 서서벌타정가이감경apoE-/-소서동맥죽양경화모형중적지질침적화염증반응,가이증가기효원함량,리우반괴적은정,구유항동맥죽양경화적작용,대혈지무영향.
Objective To investigate the effect of rosuvastatin on atherosclerosis in apoE-knockout ( apoE - / - ) mice. Methods Eighteen 6-week-old apoE - / - mice fed with high fat diet were used as atherosclerosis models, twelve 6-week-old C57BL/6 mice fed with normal diet were used as control. After twelve weeks, six apoE -/ - mice were used to observe the formation of atherosclerosis. Another 12 apoE -/- mice were divided into placebo treated group (n =6) and rosuvastatin group (n =6,10 mg· kg-1 ·d -1 per gavage) and treated for 12 weeks. Then, blood was collected for measuring lipid, aorta was prepared for morphologic study (HE, Oil red O, Masson) and immunohistochemical analysis (α-smooth activor protein, transforming growth factor β1, macrophage surface molecule-3 ). Results Serum cholesterol and low density lipoprotein levels were significantly higher in apoE -/- mice fed with high fat diet than in C57/ BL6 mice( all P ＜0. 01 )while triglyceride level was similar between the two groups, these were not affected by rosuvastatin. Similarly, atherosclerotic lesion area in apoE -/ - mice fed with high fat diet was also not significantly reduced by rosuvastatin, while lipid deposition could be significantly reduced and collagen deposition could be significantly increased in the aortic atherosclerotic lesions by treatment with rosuvastatin.Upregulated TGF-β1 and Mac-3 expression in the aortic atherosclerotic lesions in apoE -/- mice fed with high fat diet could also be significantly reduced by rosuvastatin (all P ＜ 0. 01 ), suggesting reduce inflammatory responses in the atherosclerotic lesion and stable atherosclerotic plaque post rosuvastatin treatment. Conclusion Reducing inflammatory responses and stabilizing plaque properties might contribute to the anti-atherosclerosis effects of rosuvastatin in mice high fat diet fed apoE -/- mice.