辛伐他汀对NF-κB-DNA结合活性和表达的影响

Effects of simvastatin on NF-kappaB-DNA binding activity and expression in atherosclerotic plaque in rabbits

目的观察辛伐他汀对兔动脉粥样硬化(AS)斑块中核因子-κB(NF-κB)-DNA结合活性及其表达的影响,进一步探讨辛伐他汀抗AS的作用机制。方法将36只雄性新西兰大耳白兔随机分为正常对照组(NC)、高脂对照组(HC)和辛伐他汀组(HC+S)。实验中动态观察血清总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C)的变化;实验结束时,用电泳移动迁移技术(EMSA)检测3组兔主动脉组织中NF-κB-DNA结合活性;用免疫组化技术观察各组血管组织中NF-κB的表达;显微镜下测定各组主动脉内膜厚度与斑块面积。结果用药后4、8、12周时,(HC+S)组的TC、TG、LDL-C水平显著低于HC组(P<0.05),但高于NC组(P<0.05);(HC+S)组的NF-κB-DNA结合活性及其表达强于NC组(P<0.05),但弱于HC组(P<0.05);(HC+S)组的AS斑块面积及血管内膜厚度均大于NC组(P<0.05),但小于HC组(P<0.05)。结论辛伐他汀可以抑制NF-κB-DNA结合活性及其表达,减轻AS的形成。

AIM To observe the effects of simvastatin on nuclear factor-kappaB （NF-κB） -DNA binding activity and expression in atherosclerotic plaque of rabbits and to explore the mechanism of simvastatin in reducing atherosclerosis. METHODS Thirty-six male New Zealand white rabbits were randomly divided into normal-Cholesterol control group （NC）, high-Cholesterol control group （HC） and high-Cholesterol ＋ simvastatin group （ HC ＋ S）. The levels of serum total cholesterol （ TC ）, triglyceride （TG） and Low density lipoprotein cholesteerol （LDL-C） were examined throughout the experiment. The NF-κB-DNA binding activity was measured with electrophoretic mobility shift assay （EMSA） and the expression of NF- κB in the rabbit aorta was detected with immunohistochemistry staining. The aortic plaque acreage and intimal thickness of aorta were measured with microscopy. RESULTS At the end of g, 8 and 12 weeks, the levels of TC, TG and LDL-C in the （ HC ＋ S） group were significantly higher than those in the NC group, but significantly lower than those in the HC group（P 〈 0.05）. At the end of experiment, the NF-κB-DNA binding activity and the expression of NF-κB in the （ HC ＋ S） group were significantly higher than those in the NC group, but significantly lower than those in the HC group （ P 〈 0.05 ）. The aortic plaque acreage and intimal thickness in the （ HC ＋ S） group were significantly higher than those in the NC group, but significantly lower than those in the HC group （ P 〈 0.05 ）. CONCLUSION This study demonstrates that simvastatin inhibits NF-κB-DNA binding activity, reduces the expression of NF- κB protein and decreases atherosclerosis.