瑞舒伐他汀对载脂蛋白E基因敲除小鼠动脉粥样硬化的影响

Impact of rosuvastatin on atherosclerosis lesions in apolipoprotein E knockout mice

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10mg·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。

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 （eL-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/ BI/5 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 T,osuvastatin. 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.