Effects of Simvastatin on NF-κB-DNA Binding Activity and Monocyte Chemoattractant Protein-1 Expression in a Rabbit Model of Atherosclerosis / 华中科技大学学报（医学）（英德文版）

ABSTRACT

To observe the effects of simvastatin on nuclear factor kappaB (NF-κB)-DNA binding activity and on the expression of monocyte chemoattractant protein-1 (MCP-1) in atherosclerotic plaque in rabbits and to explore the anti-atherosclerotic properties beyond its lipid-lowering effects.Thirty-six New Zealand male rabbits were randomly divided into low-cholesterol group (LC), highcholesterol group (HC), high-cholesterol+ simvastatin group (HC+S) and then were fed for 12weeks. At the end of theexperiment, standard enzymatic assays, electrophoretic mobility shift assay (EMSA), immunohistochemical staining, and morphometry were performed to observe serum lipids, NF-κB-DNA binding activity, MCP-1 protein expression, intima thickness and plaque area of aorta respectively in all three groups. Our results showed that the serum lipids, NF-κB-DNA binding activity, expression of MCP-1 protein, 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 serum lipids 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 significantly decreased as compared to the LC group (P＜0.05). This study demonstrated that simvastatin could decrease atherosclerosis by inhibiting the NFκB-DNA binding activity and by reducing the expression of MCP-1 protein.