阿托伐他汀对兔动脉粥样硬化斑块的干预作用

目的：探讨阿托伐他汀对实验兔动脉粥样硬化模型血脂、血清血管内皮生长因子（VEGF）水平及动脉粥样斑块内VEGF蛋白水平的影响。方法20只雄性新西兰大白兔，按随机数字表法等分为对照组、模型组、低剂量他汀组和高剂量他汀组，其中对照组采用普通饲料喂养，后3组均采用高脂饲料喂养，4w后行腹主动脉球囊损伤，模型组不加其他处理，低剂量他汀组予5 mg/（kg.d），高剂量他汀组予10 mg/（kg.d）。分别于0w、6w和12w检测各组血清甘油三酯（TG）、胆固醇（TC）、低密度脂蛋白（LDL-C）、血管内皮生长因子（VEGF）水平，12w后行腹主动脉HE染色观察动脉粥样硬化改变，检测斑块内VEGF蛋白和VEGF mRNA的表达。结果与对照组相比，模型组、低剂量他汀组、高剂量他汀组在6w和12w的血LDL-C、TG、TC、VEGF均显著增高（P＜0.01）。与模型组比较，他汀组血LDL-C、TG、TC、VEGF在第6w和12w有明显降低，但高剂量他汀组降低更为明显（P＜0.05）；同时，他汀组动脉粥样硬化斑块中VEGF蛋白和mRNA表达均下降。结论阿托伐他汀可降低兔动脉粥样硬化模型的血脂水平，且呈剂量依赖性；同时还可下调AS斑块内VEGF的表达水平。

Intervention effect of atorvastatin on vascular endothelial growth factor in atherosclerotic plaque in rabbits

Objective To investigate the influences of atorvastatin on levels of blood fat, vascular endothelial growth factor （VEGF） and expression of VEGF protein in rabbit model of atherosclerosis.Methods Male New Zealand rabbits （n=20） were divided into control group, model group, low-dose atorvastatin group and high-dose atorvastatin group according to random digits table. The control group was fed normal fodder, and other three groups were fed fatty fodder. After 4 w, low-dose atorvastatin group was given 5 mg/（kg.d） atorvastatin and high-dose atorvastatin group was given 10 mg/（kg.d）. The levels of serum TG, TC, LDL-C and VEGF were detected on the 0 w, 6th w and 12th w respectively. After 12 w, the changes of atherosclerosis were observed and expressions of VEGF protein and VEGF mRNA in atherosclerotic plaques were detected after HE staining.Results Compared with control group, the levels of LDL-C, TG, TC and VEGF increased significantly in other three groups （P〈0.01） on the 6th w and 12th w. Compared with model group, the levels of LDL-C, TG, TC and VEGF decreased significantly in two atorvastatin groups on the 6th w and 12th w, which were more significant in high-dose atorvastatin group （P〈0.05）. At the same time, the expressions of VEGF protein and VEGF mRNA all decreased atherosclerotic plaques.Conclusion Atorvastatin can reduce the level of blood fat showing a dose-dependence, and down-regulate the expression of VEGF in atherosclerotic plaques.