罗格列酮联合阿托伐他汀对高胆固醇血症兔主动脉斑块面积和TNF-α的影响

Effects of rosiglitazone and atorvastatin alone or combination on aortic atherosclerotic area and TNF-α in hypercholesterolemic rabbits

目的:观察罗格列酮和阿托伐他汀单独或联合应用对高胆固醇血症兔主动脉斑块面积和TNF-α的影响。方法:24只雄性新西兰大白兔高胆固醇饮食8周后,随机加喂淀粉(淀粉组,n=6)或阿托伐他汀(阿托伐他汀组,5mg·kg-1·d-1,n=6)或罗格列酮钠(罗格列酮组,3mg·kg-1·d-1,n=6)或罗格列酮钠联合阿托伐他汀(联合组,阿托伐他汀钙5mg·kg-1·d-1、罗格列酮3mg·kg-1·d-1,n=6)喂养4周。以普通饲料喂养兔作为正常对照(对照组,n=6)。各组兔共喂养12周后,取兔主动脉测定内膜斑块面积,同时分离外周血单核细胞培养24h,采用酶联免疫吸附测定法检测血浆和单核细胞细胞培养上清液TNF-α。结果:与对照组相比,高胆固醇饮食各组兔血浆和外周血单核细胞TNF-α水平升高(均P<0.01);与淀粉组相比,阿托伐他汀和罗格列酮体内干预都能降低高胆固醇血症兔主动脉斑块面积百分数、血浆和外周血单核细胞TNF-α水平,且二者联合干预降低程度更显著(P均<0.01);兔主动脉斑块面积与血浆/外周血单核细胞TNF-α水平呈显著正相关(均P<0.01)。结论:阿托伐他汀和罗格列酮可能通过抑制外周血单核细胞分泌TNF-α发挥抗动脉粥样硬化(AS)作用,且二者联合应用效果更佳。

AIM： To investigate the effects of rosiglitazone and atorvastatin alone or combination on aortic atherosclerotic area and TNF-α synthesis in hyper- cholesterolemie rabbits. METHODS：Thirty male New Zealand rabbits were randomly divided into normal diet group （ n = 6） and high-cholesterol diet group （ 1% cholesterol diet, n = 24）. After 8 weeks, hypercholes- terolemic rabbits were randomly fed with starch （starch group, n = 6 ）, atorvastatin （ atorvastatin group, 5 mg·kg-1·d-1, n = 6 ） or rosiglitazone （ rosiglitazone group, 3 mg·kg-1·d-1, n = 6 ）, rosiglitazone plus atorvastatin [ eombination group, atoi＇vastatin （ 5 mg·kg-1·d-1 ）, rosiglitazone （ 3 mg·kg-1·d-1 ）, n = 6]. Four weeks later, all rabbits were killed, and monoeytes were isolated from peripheral blood mono- eytes of these rabbits, then were cultured for 24 hours. TNF-a antigens in plasm and monoeytes were measured by enzyme -linked immunosorbent assay. RESULTS： Compared with normal diet group, levels of TNF-α were increased in plasma and monocytes of high-cholesterol diet groups. Compared with starch group, the area of atherosclerotic lesions and the levels of TNF-α in plas- ma and monocytes of hypercholesterolemic rabbits were decreased in rosiglitazone , atorvastatin, or rosiglitazone plus atorvastain groups, furthermore, which had a more significant reduction in rosiglitazone plus atorvastain group （P 〈 0.01 ）. There was a positive correlation between the area of atherosclerotic lesions and the levels of TNF-α in plasm and monocytes （ P 〈 0.01 ）. CONCLUSION： Atorvastatin combined with rosiglita- zone assuage atherosclerosis through suppressing TNF-α secretion in peripheral blood monocytes. Synergistic administration of rosiglitazone and atorvastatin exerts a better anti-atheromatous effect.