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

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 atherosclerotic plaque in rabbits and to explore the mechanism of simvastatin possessing antiatherosclerotic 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). Immunohistochemistry 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(P0.05). There was no significant difference in the levels of TC,TG ,LDL-C between the LC and HC+S groups(P0.05),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(P0.05). Conclusion This study demonstrates that simvastatin could decrease atherosclerosis by inhibiting NF-κB-DNA binding activity and reducing the expression of MCP-1.