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

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(P0.05).There was no significant difference in the serum lipids between the LC group and HC+S group(P0.05),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(P0.05). 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.