阿托伐他汀钙对兔动脉粥样硬化的影响

The effect of atorvastatin calcium on artherosclerosis in rabbits

目的观察阿托伐他汀钙对兔动脉粥样硬化血管内皮的保护作用。方法将30只4月龄雄性健康日本大耳白兔,随机分为3组,每组10只。空白对照组:给予普通饲料喂养;模型组:给予高脂饲料喂养(高脂饲料配方:1%胆固醇(TC)+10%猪油+7.5%蛋黄粉+81.5%普通饲料);治疗组:在给予高脂饲料喂养的同时加用阿托伐他汀钙5mg.kg-1.d-1。实验共进行12周。实验结束时,处死动物取血测定TC、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、血清一氧化氮(NO)和内皮素-1(ET-1)水平,取主动脉进行病理学观察。结果与空白对照组比较,模型组、治疗组兔的血清TC、TG、LDL-C、ET-1水平显著升高(P<0.01),而HDL-C、NO水平显著降低(P<0.01);模型组兔血管内膜明显增厚,形成动脉粥样硬化斑块,内含大量泡沫细胞,具有典型的动脉粥样硬化表现;与模型组相比,治疗组兔血清TC、TG、LDL-C、ET-1水平显著降低(P<0.01),而HDL-C、NO水平显著升高(P<0.01);兔血管内膜轻度增厚,有较少量泡沫细胞,动脉粥样硬化病变程度较模型组明显减轻。结论阿托伐他汀钙除具有强大的降脂作用外,还通过升高NO水平降低ET-1水平,改善血管内皮功能发挥抗动脉粥样硬化作用。

Objective To observe the protective effect of atorvastatin calcium on atherosclerotic vascular endothelial in rabbits.Methods 30 healthy male Japanese rabbits at 4 months age were randomly divided into 3 groups,10 rabbits in each group.The rabbits in control group were fed with common diet;the rabbits in model group were fed with high fat diet（high fat diet ingredient：1% cholesterol and 10% lard ＋ 7.5% egg yolk powder ＋ 81.5% common forage） ;the those in treatment groups were fed with high fat diet and atorvastatin calcium 5mg.kg-1.d-1.All the rabbits were fed for 12 weeks.At the end of the experiment,all the rabbits were killed.The blood samples were collected for measuring the levels of serum lipids,NO,ET-1,and the artery was obtained to be observed pathologically.Results As compared with those in control group,the levels of serum TC,TG,LDL-C,ET-1 were increased significantly,while the levels of serum HDL-C,NO were decreased significantly in model group and treatment group（P 〈0.01）.The vessels intima was severely thicken and the atherosclerotic plaque was formed,which contained a large number of foam cells,with typical performance of atherosclerosis in model group.As compared with those in model group,the levels of serum TC,TG,LDL-C,ET-1 were reduced significantly,while the levels of serum HDL-C,NO were increased significantly（P 〈0.01）.The vessels intima was slightly thicken,with less amount of foam cells and atherosclerotic degree was significantly reduced in treatment group.Conclusion In addition to a powerful lipid-lowering function,atorvastatin calcium can improve endothelial function and prevent the development of atherosclerosis by increasing NO levels and decreasing ET-1 levels.