氟伐他汀对兔动脉粥样硬化血管壁NF-κB及ICAM-1表达的影响

Effect of fluvastatin on the expression of NF-κB and ICAM-1 in the blood vessel wall of atherosclerosis rabbits

目的:观察氟伐他汀对动脉粥样硬化(As)家兔模型血管壁核因子-kappaB(NF-κB)活性及mRNA、细胞间粘附分子-1(ICAM-1)表达的影响,以探讨氟伐他汀抗As的作用机制。方法:雄性新西兰家兔32只,随机分为对照组、高脂饮食组、氟伐他汀组。喂养12周后处死动物并留取主动脉标本,观察组织形态学变化,用免疫组化法观察NF-κB活性、ICAM-1表达,用原位杂交法观察NF-κBmRNA表达。结果:氟伐他汀组与高脂饮食组相比,As病变明显减轻(P<0.01);NF-κB活性由(40.3±5.9)%减弱为(17.3±2.4)%(P<0.01);NF-κBmRNA表达由(41.7±5.5)%减弱为(19.6±1.7)%(P<0.01);ICAM-1表达由(31.6±2.7)%减弱为(16.5±2.1)%(P<0.01)。结论:氟伐他汀抗As作用与抑制NF-κB活性,下调ICAM-1表达有关。

Objective: To observe the effect of fluvastatin on the activity of nuclear factor kappa B(NF-κB), the expressions of NF-κB mRNA and intercellular adhesion molecule -1 (ICAM-1)in the blood vessel wall of atherosclerosis (As) rabbits. Methods: Thirty-two healthy male New Zealand rabbits were divided randomly into control group, high fat diet group and fluvastatin group. They were fed for 12 weeks to build atherolerosis model and observed the formation of As plaque through aorta tissue. The activity of NF-κB and the expression of ICAM-1 were detected in immunohistochemical method and the mRNA expression of NF-κB was detected in situ hybridization. Results: The abnormality of atherosclerosis in fluvastatin group was more mitigative than that in high fat diet group (P<0.01). With fluvastatin, the activity of NF-κB was cut from (40.3±5.9)% to (17.3±2.4) % (P<0.01); the mRNA expression of NF-κB from (41.7±5.5)% to (19.6±1.7) % (P<0.01); the expression of ICAM-1 from (31.6±2.7)% to (16.5±2.1)% (P<0.01). Conclusion: The anti-atherosclerosis mechanism of fluvastatin is relevant to inhibiting the activation of NF-κB and down-regulation of the expression of ICAM-1.