辛伐他汀对兔动脉粥样硬化斑块中核因子κB-DNA结合活性和基质金属蛋白酶1及3表达的影响
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国家自然科学基金(30470713)资助


Effects of Simvastatin on Nuclear Factor κB-DNA Binding Activity and Matrix Metalloproteinase-1 and 3 Protein Expression in Atherosclerosis Model of Rabbit
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    摘要:

    目的观察辛伐他汀对兔动脉粥样硬化斑块中核因子κB-DNA结合活性和基质金属蛋白酶1及3表达的影响,进一步探讨辛伐他汀降脂效应以外的抗动脉粥样硬化作用机制。方法36只雄性新西兰大耳白兔被随机分为低脂对照组、高脂对照组和辛伐他汀组,喂养12周。实验结束时,分别用酶标法、电泳移动迁移技术、免疫组织化学和形态学方法观察三组兔的血脂水平、主动脉组织中核因子κB-DNA结合活性、基质金属蛋白酶1和3的表达及血管内膜厚度。结果实验结束时,低脂对照组和辛伐他汀组血脂水平、核因子κB-DNA结合活性、基质金属蛋白酶1和3的表达及血管内膜厚度均明显低于高脂对照组(p<0.05);辛伐他汀组血脂水平与低脂对照组相比无明显差异,但核因子κB-DNA结合活性、基质金属蛋白酶1和3的表达及血管内膜厚度均明显低于低脂对照组(p<0.05)。结论辛伐他汀可以抑制核因子κB-DNA结合活性,减弱基质金属蛋白酶1和3的表达,延缓动脉粥样硬化的形成。

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    Aim To observe the effects of simvastatin on nuclear factor-κB(NF-κB)-DNA binding activity and on the expression of matrix metalloproteinase(MMP)-1 and 3 in atherosclerotic plaque in rabbits and to explore the anti-atherosclerotic properties beyond its lipid-lowering effects. Methods Thirty-six New Zealand male rabbits were randomly divided into low cholesterol group(LC),high cholesterol group(HC),high cholesterol+simvastatin group(HC+S),and then were fed for 12 weeks.At the end of experiment,standard enzymatic assay,electrophoretic mobility shift assay(EMSA),immunohistochemistry staining,and morphometry were performed to observe serum lipids,NF-κB-DNA binding activity,MMP-1 and 3 protein expression,intima thickness and plaque area of aorta respectively in all three groups. Results The serum lipids,NF-κB-DNA binding activity,expression of MMP-1 and 3 protein and intima thickness of aorta in the LC group and HC+S group were significantly lower than those in the HC group(p<0.05).There was no significant difference in the serum lipids between the LC group and HC+S group(p<0.05),but the NF-κB-DNA binding activity,the expression of MMP-1 and 3 protein and the intima thickness of aorta in the HC+S group were significantly decreased compared with the LC group(p<0.05). Conclusions This study demonstrates that simvastatin could inhibit the NF-κB-DNA binding activity,reduce the expression of MMP-1 and 3 protein,and decrease atherosclerosis.

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杨晓云,王琳,曾和松,周宁,卜军,袁永辉.辛伐他汀对兔动脉粥样硬化斑块中核因子κB-DNA结合活性和基质金属蛋白酶1及3表达的影响[J].中国动脉硬化杂志,2006,14(4):277~280.

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  • 收稿日期:2005-06-10
  • 最后修改日期:2006-04-10
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