辛伐他汀对动脉粥样硬化家兔血管壁NF-κB-DNA结合活性与MCP-1表达的影响

Effects of Simvastatin on Nuclear Factor KappaB-DNA Binding Activity and Monocyte Chemoattractant Protein-1 Expression in Atherosclerotic Plaque in Rabbits

目的观察辛伐他汀对兔动脉粥样硬化斑块中核因子-κB(NF-κB)-DNA结合活性与单核细胞趋化因子-1(MCP-1)表达的影响,探讨辛伐他汀降脂效应以外的抗动脉粥样硬化(AS)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(LC)、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)检测三组兔主动脉组织中NF-κB-DNA结合活性;用免疫组化技术观察各组血管组织中MCP-1的表达;显微镜下测定各组主动脉内膜厚度与粥样斑块面积。结果实验结束时,HC+S与LC组的TC、TG、LDL-C水平、NF-κB-DNA结合活性、MCP-1表达、主动脉内膜厚度和粥样斑块面积均明显小于HC组(P<0.05);HC+S组的的TC、TG和LDL-C水平与LC组相比虽无明显差异(P>0.05),但其NF-κB-DNA结合活性、MCP-1表达、内膜厚度和粥样斑块面积均小于LC组(P<0.05)。结论辛伐他汀可以通过抑制NF-κB-DNA结合活性、减弱MCP-1表达而减轻AS的形成。

Objective To observe the effects of simvastatin on nuclear factor- kappaB （NF-κB） -DNA binding activity and on expression of monocyte chemoattractant protein-1（MCP-1） in atheroclerotic plaque in rabbits and to explore the mechanism of simvastatin possessing antiatherceclerotic activities independent of their lipid-lowering action. Methods 36 male New Zealand white rabbits were randomly divided into low-cholesterol control group（LC）, high-cholesterol control group（HC） and high-cholesterol ＋ simvastatin group（ HC ＋ S）. During the experiment, the levels of TC, TG and LDL-C were examined. The method for detection of NF-κB- DNA binding activity in the aorta of three groups was electrophoretic mobility shift assay （ EMSA）. Immunohistechemistry staining was used to examine the expression of MCP-1 in the aorta of rabbit. The intima thickness and plaque area of aorta was measured with microscopy. Results At the end of experiment, the levels of TC, TG, LDL-C, the NF-κB-DNA binding activity, the expression of MCP-1, the intima thickness and plaque area of aorta in the LC and HC ＋S groups were significantly lower than those in the HC group（P〈0.05）. There was no significant difference in the levels of TC, TG, LDL-C between the LC and HC ＋ S groups（ P〉0.05）, but the NF-κB-DNA binding activity, the expression of MCP-1 protein and the intima thickness and plaque area of aorta in the HC ＋ S group were decreased compared with those in LC group（P〈0.05）. Conclusion This study demonstrates that simvastatin could decrease atherosclerosis by inhibiting NF-κB-DNA binding activity and reducing the expression of MCP-1.