氟伐他汀对兔动脉粥样硬化血管壁NF-κB和PDGF表达的影响

Effect of fluvastatin on the expression of NF-κB and PDGF-A 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)、血小板源性生长因子-A(PDGF-A)表达及血管平滑肌细胞(SMC)增殖的影响,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、PDGF-A蛋白及SMC增殖细胞核抗原(PCNA)表达,用原位杂交法观察NF-κBmRNA表达,应用RT-PCR检测PDGF-AmRNA表达。结果:氟伐他汀组与高脂饮食组比较,AS病变明显减轻(P<0.01);PCNA表达由(29.8±3.0)%减弱为(13.5±4.5)%(P<0.01);PDGF-A表达由(73.9±6.2)%减弱为(46.9±4.2)%(P<0.01)。PDGF-AmRNA表达由(0.73±0.019)减弱为(0.50±0.028)(P<0.01)。NF-κB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)。PDGF-A蛋白表达与PCNA表达呈正相关(P<0.05);NF-κB与PDGF-A蛋白表达呈正相关(P<0.05)。结论:氟伐他汀抗AS的形成,抑制SMC增殖,其作用机制可能与抑制NF-κB活性、下调PDGF-A表达有关。

Objective： To observe the effect of fluvastatin on the expressions of nuclear factor kappa B（ NF-κB）,and platelet derived growth factor-A（PDGF-A）and the proliferation of blood vessel smooth muscle cell （SMC） in the blood vessel wall of atherosclerosis （AS） rabbits. Methyl：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 AS model and observed the formation of AS plaque through aorta tissue. The expression of NF-κB and PDGF-A and proliferating cell nuclear antigen （PCNA） were detected in immunohistochemical method, the mR NA expression of NF-κB was detected in situ hybridization, and the mRNA expression of PDGFA was detected by RT-PCR. Result：The abnormality of AS in fluvastatin group was more mitigative than that in high fat diet group （ P〈0.01）. With fluvastatin , the expression of PCNA decreased from （29.8±3.0）% to （13. 5±4.5）% （ P〈 0.01）; the protein expression of PDGF-A decreased from （73. 9±6. 2）% to （46. 9±4. 2）% （ P 〈0.01）; the mRNA expression of PDGF-A decreased from （0.73±0. 019）% to （0.50±0. 028）% （ P 〈0.01） ; the expression of NF-κB decreased 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 protein expression of PDGF-A are positive associated with the expression of PCNA in every group（ P 〈0.05）. There are positive association between NF-κB activity and the pro- tein expression of PDGF-A separately in every group （ P 〈0.05）. Conclusion：Fluvastatin have the effect of anti-AS and can inhibit the proliferation of SMC. The anti-AS mechanism of fluvastatin maybe relevant to inhibiting the activation of NF-κB and down regulation of the expression of PDGF A and then inhibiting the proliferation of SMC.