阿司匹林抗动脉粥样硬化作用的机制探讨  

Antiatherosclerotic mechanism of aspirin:experiment with rabbits

作　　者：杨晓云[1] 王琳[1] 周宁[1] 曾和松[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院心内科,武汉430030

出　　处：《中华医学杂志》2007年第46期3298-3301,共4页National Medical Journal of China

基　　金：国家自然科学基金(30470713)

摘　　要：目的观察阿司匹林对动脉粥样硬化(AS)家兔血管壁核因子-kB(NF-kB)-DNA 结合活性、环氧化酶-2(COX-2)蛋白表达、AS 斑块面积和血管内膜厚度的影响,探讨阿司匹林的抗 AS 作用机制。方法36只雄性新西兰大耳白兔被随机分为正常对照组(NC)、高脂对照组(HC)和阿司匹林组(HC+A)。实验结束时,分别用酶法、固相酶联免疫吸附实验、电泳移动迁移技术、免疫组化技术、形态学方法检测3组兔的血脂、高敏 C 反应蛋白(hs-CRP)水平、主动脉组织中 NF-kB-DNA 结合活性、COX-2蛋白表达及各组主动脉新生内膜厚度和 AS 斑块面积。结果 HC 与 HC+A 组的血脂和 hs-CRP 水平、NF-kB-DNA 结合活性、COX-2蛋白表达、动脉新生内膜厚度和粥样斑块面积均明显大于 NC 组(P<0.05～0.01);HC+A 组的血脂水平与 HC 组相比差异无统计学意义(P>0.05),但HC+A 与 HC 组的 hs-CRP 水平[(5.14±0.32)μg/ml vs(9.39±0.79)μg/ml,P<0.05]、NF-kB-DNA 结合活性[(14.6±2.7)μg/ml vs(32.4±4.7)μg/ml,P<0.05]、COX-2蛋白表达[(0.342±0.02 vs 0.572±0.061,P<0.05)]、血管新生内膜厚度[(165±24)μm vs(337±64)μm(P<0.05)]和 AS 斑块面积[(24.3±7.6)%vs(49.5±21.3)%,(P<0.05)]相比差异有统计学意义。结论阿司匹林可通过抑制 NF-kB-DNA 结合活性、降低 hs-CRP 水平、减弱 COX-2蛋白表达而发挥抗 AS 作用。Objective To observe the effects of aspirin on nuclear factor kappaB （NF-κB）-DNA binding activity and on the expression of cyclooxygenase-2 （COX-2）in atherosclerotic plaque so as to explore its antiatherosclerotic mechanism. Methods Thirty-six New Zealand male rabbits were randomly divided into 3 equal groups ： high-cholesterol （ HC ） group, fed with food high in cholesterol and perfused into the empty stomach daily with distilled water for 12 weeks, high-cholesterol and aspirin （ HC ＋ A） group, fed with food high in cholesterol and perfused into the empty stomach daily with aspirin solution, and normal control （NC） group, fed with normal food and perfused into the empty stomach daily with distilled water, before the experient, and 4, 8, and 12 weeks after the beginning of experiment peripheral blood samples were collected. The serum lipids were detected with enzymatic assays; and enzyme-linked immunosorbent assay was used to detect the level of high sensitive C-reactive protein （hs-CRP）. By the end of experiment the rabbits were killed to take out the specimens of aorta to observe the neointima thickness and plaque area of aorta. Electrophoretic mobility shift assay was used to detect the NF-κB-DNA binding activity, and immunohistochemistry and morphometry were performed to observe the expression of COX-2 protein, the neointima thickness and plaque area of aorta respectively in all three groups. Results The levels of serum lipids, hs-CRP, NF-κB-DNA binding activity, expression of COX-2 protein, and neointima thickness and plaque area of aorta in the HC and HC ＋ A groups were all significantly higher than those in the NC group （ P 〈 0.05 - 0.01 ）. There was no significant differences in the serum lipids between the HC and HC ＋ A groups （ all P 〉0.05）, however, the levels of hs-CRP, NF-KB-DNA binding activity, expression of COX-2 protein, and neointima thickness and plaque area of aorta of the HC ＋ A group were （5.14±0.32）μg/ml, （14.6±2.7）μg/ml, （0.342

关 键 词：动脉粥样硬化 阿司匹林 环氧化酶-2 核因子-ΚB 

分 类 号：R96[医药卫生—药理学]