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

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

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。

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 atberosclerotic plaque in rabbits and to explore the anti-atherosclerotic properties beyond its lipid-lowering effects. MeThods Thirty-six New Zealand male rabbits were randomnly 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, electrophoretie mobility shift assay （EMSA）, immunohistchenistry 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.