阿托伐他汀、氯吡格雷、普罗布考合用对兔动脉粥样硬化病变进展的抑制作用

Inhibitory effects of the combination of Atorvastain,Clopidogrel and Probucol on the progression of atherosclerosis in rabbits

目的:观察阿托伐他汀、氯吡格雷、普罗布考合用对兔动脉粥样硬化病变进展的抑制作用。方法:将47只雄性新西兰白兔随机分为正常对照组(A组,n=9)及高脂饮食组(N组,n=38)。高脂饮食组以1%胆固醇饲料喂养6周,6周后随机抽取2只,观察主动脉组织病理形态,以明确动脉粥样斑块形成。6周时高脂饮食组依据兔子体重随机分为高脂组(高脂饮食)(B组,n=12)、阿托伐他汀组[高脂饮食+阿托伐他汀5mg/(kg·d)](C组,n=12)、联合治疗组[高脂饮食+阿托伐他汀5mg/(kg·d)+氯吡格雷10mg/(kg·d)+普罗布考0.25g/(kg·d)](D组,n=12),药物与高脂饮食同步干预。实验前、实验6、14周取血清,测定血脂(TC、TG、LDL、HDL)浓度。14周时取胸主动脉行苏木精-伊红染色(HE),测定内膜、中膜厚度及粥样斑块面积;免疫组化测定IL-6的阳性细胞百分比,染色结果行定量分析。结果:高脂饮食各组血脂显著增高,主动脉见典型脂质条纹,局部斑块形成,病变处IL-6显著表达。与单纯高脂组相比,①阿托伐他汀组、联合治疗组主动脉内膜增厚显著减轻,粥样斑块面积缩小(P<0.05),联合治疗组则更为明显(P<0.01)。②阿托伐他汀及联合治疗组均能降低斑块中IL-6百分数,联合治疗组更为显著,两者比较,有显著性差异。③阿托伐他汀及联合治疗组均能降低血清胆固醇水平,但两者无显著性差异。结论:阿托伐他汀、氯吡格雷及普罗布考均有抑制内膜增生和动脉粥样硬化病变进展的作用,联合使用抗动脉粥样硬化效果更佳。

Objective： To observe the inhibitory effects of the combination Atorvastain, Clopidogrel and Probucol on the progression of atheroselerosis in rabbits. Methods： 47 male New Zealand white rabbits were randomly divided into two groups： normal control group （group A, n=9） and high fat diet group （group N, n=38）. The high fat diet group was fed on 1% cholesterol for six weeks. After six weeks, two rabbits were randomly selected and killed, then the aorta tissue pathological morphology was observed to identify the development of atheroselerosis plaque. At the sixth week, the rabbits in high fat diet group were randomly divided into three groups： high fat group （group B, n=12 ）, Atorvastain group [group C, high-cholesterol diet with 5 mg/（kg·d） Atorvastain, n=12], combination therapy group [group D, high-cholesterol diet with 5 mg/（kg.d） Atorvastain, 10 mg/（kg·d） Clopidogrel and 0.25 mg/（kg·d） Probueol, n=12]. Blood was drawn to determine the blood fat concentration （TG, TC, HDL, LDL） before experiment, 6 and 14 weeks after administrating drugs. All the rabbits aortas were collected for pathological sections by hematoxylin-eosin （HE）, image analysis was performed to measure the thickness of intima and media, and the area of atheromatous plaque. The positive percentage of IL-6 cells and smooth muscle cells in the plaque was analyzed by immunohistochemistry. The staining result was developed quantitative analysis. Results： The blood fat levels in all high fat diet groups were significantly increased, the typical fatty streaks and early atheromatous plaque on the aorta were formed and the expression of IL-6 in the lesion were significantly increased. Compare with the single high fat group, the thickness of intima and media, and the area of atheromatous plaque were lower in Atorvastain group and combination therapy group （P〈〈0.05）, especially in combination group （P〈0.01）. There was a decrease of the expression of IL-6 in the Atorvastain group and combination therapy group, while the expression was reduced remarkably in combination therapy group. Serum cholesterol level was reduced remarkably in the Atorvastain group and combination therapy group, and there was no significant difference between the two groups. Conclusion： Atorvastain, Clopidogrel and Probucol can inhibit the intimal proliferation and prevent the development of atheroselerosis. The combination of the three drugs shows better effect.