辛伐他汀联合依折麦布对ApoE^(-/-)小鼠动脉粥样硬化的影响

Effect of combined simvastatin and ezetimibe on atherosclerosis in ApoE^(-/-) mice

目的观察辛伐他汀联合依折麦布对高脂喂养的ApoE-/-小鼠动脉粥样硬化斑块的作用。方法选取8周龄雄性AopE-/-小鼠36只,随机分为模型组、辛伐他汀组和联合组,辛伐他汀组给予辛伐他汀20 mg/kg灌胃,联合组给予20 mg/kg辛伐他汀和10 mg/kg依折麦布灌胃,模型组给予等量磷酸盐缓冲液(PBS)灌胃。灌胃1次/d,连续8周后,取主动脉全程进行油红O染色,计算斑块面积百分比。结果辛伐他汀组及联合组的血清甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)和低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)水平明显低于模型组(P<0.01),其中联合组TG和LDL-C水平降低更明显(与辛伐他汀组比较,P<0.01),联合组HDL-C/LDL-C比值较模型组和辛伐他汀组明显升高(P<0.001)。辛伐他汀组和联合组主动脉斑块面积百分比显著小于模型组(P<0.05),联合组减小更显著(P<0.01)。结论辛伐他汀联合依折麦布对动脉粥样硬化的抑制作用更明显。

Objective To study the effect of combined simvastatin and ezetimibe on atherosclerosis in ApoE-/- mice on a high-fat diet. Methods Thirty-six male ApoE-/-mice aged 8 weeks were randomly divided into model group, simvastatin treatment group and combined simvastatin and ezetimibe treatment group （12 in each group）. Animals in simvastatin treatment group were treated with intragastric simvastatin （20 mg/kg）, those in combined simvastatin and ezetimibe treatment group were treated with intragastric simvastatin （20 mg/kg） and ezetimibe （10 mg/kg）, and those in model group received PBS buffer, once a day for 8 weeks. Aorta tissue sample taken from the animals were stained with oil red O to measure the area of their plaques. Results The serum TG, TC and LDL-C levels were significantly lower in simvastatin treatment group and combined simvastatin and ezetimibe treatment group than in model group （P 〈 0.01）. The serum TG and LDL-C levels were significantly lower in combined simvastatin and ezetimibe treatment group than in simvastatin treatment group （P 〈 0.01） whereas the HDL-C/LDL-C ratio was significantly higher in combined simvastatin and ezetimibe treatment group than in model group and simvastatin treatment group （P 〈 0.01）. The area of plaques was significantly smaller in simvastatin treatment group and combined simvastatin and ezetimibe treatment group than in model group （P 〈 0.01）. Conclusion Combined simvastatin and ezetimibe inhibits atherosclerosis in ApoE-/- mice more significantly than simvastatin alone.