阿托伐他汀对兔动脉粥样硬化形成中血管内皮细胞黏附分子-1表达变化的影响

目的 探讨动脉粥样硬化（AS）时血管内皮细胞黏附分子-1（VCAM—1）表达及阿托伐他汀干预作用。方法取88只新西兰纯种雄性大白兔,随机分为3组：对照组（C组）24只,喂以正常饲料;模型组（AS组）32只,喂以高脂饲料;阿托伐他汀组（D组）32只,除高脂饮食外,同时予阿托伐他汀灌胃。分别于2、4、6、8周末随机抽取6～8只处死,采血检测血脂,取胸主动脉制作标本,应用免疫组化检测VCAM-1的表达。结果C组血脂在实验前后无明显变化,而AS组和D组血浆血脂TC、TG、LDL水平在2、4、6、8周末时与实验前及C组相比,均显著较高;同期D组均明显低于AS组（均P〈0．01）,高于C组（均P〈0．01）。在C组胸主动脉VCAM-1无表达,AS组随时间的延长不仅内皮细胞表达增强,且斑块内和中膜平滑肌表达逐渐增强,表达范同逐渐增大;而D组胸主动脉VCAM—1免疫反应阳性范围及程度均低于同期AS组。结论VCAM-1在胸主动脉的表达随AS病变加重而增强,其参与了AS的发生和发展。他汀类药物可通过抑制黏附分子的表达发挥其抗炎作用．从而延缓AS的发生发展。

Influence of atorvastatin on the vascular cellular adhesion molecule-1 expression in atherosclerosis: experiment with rabbits

Objective To investigate the expression of vascular cellular adhesion molecule-1 （VCAM-1） in vessels during atherosclerosis and the interventional effect of atorvastatin thereupon. Methods Eighty-eight male New Zealand White rabbits were randomly divided into 3 groups： normal control group （C group, n=24, fed with standard rabbit diet）,atherosclerosis group （AS group, n=32, fed with high-fat diet）, and atorvastatin group （D group, n=32, fed with atorvastatin in addition to high-fat diet）. 2, 4, 6, and 8 samples were collected from the inferior vena cava to examine the levels of blood fat, and then the thoracic aortas were harvested. Immunohistochemistry was used to examine the expression of VCAM-1. Results There were no significant differences in the blood levels of total cholesterol （TC）, triglyceride （TG）, and low-density lipoprotein （LDL） before and after the experiment in the C group. However, the blood levels of TC, TG, and LDL 2, 4, 6, and 8 weeks later of the AS and D groups were all significantly higher than those before the experiment and those of the C group at the respective time points （all P〈0.01）, and those of the D group at any time points were all significantly lower than those of the AS group at the corresponding time points （all P〈 0.01）. Since 2 weeks later VCAM-1 espression could be seen in the epithelial cells, atheromatous plaques, and smooth muscle cells in tunica media of the AS and D groups, and the expression range and degree increased along with time. However, the range and degree of VCAM-1 expression at any time point were all obviously lighter narroweror in the D group than in the AS group. Conclusion VCAM-1 expression is upregulated with aggravating pathological changes of AS and participates in the initiation and development of atherosclerotic lesion. Atorvastatin prevents the AS develpoment by suppressing the overexpression of VCAM-1.