Objective： To investigate the mechanisms that Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A（HMG-CoA） reductase inhibitor, plays an important role in primary prevention of atherosclerosis independently of its...Objective： To investigate the mechanisms that Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A（HMG-CoA） reductase inhibitor, plays an important role in primary prevention of atherosclerosis independently of its lipid-lowering effect in Apolipoprotein E-deficient mice in the early stage of atherosclerosis. Methods： Twenty-four 6-week old male apoE-deficient mice were randomly divided into two groups：control group（normal saline） and treatment group[simvastatin（5 mg/（kg · d））]. Simvastatin was administered to treatment group mice by gavage and the same volume of normal saline was administered to control group mice by the same method for 2 or 4 weeks. Total cholesterol（TC）, super-oxide dismutase（SOD）, malondialdehyde（MDA） and serum nitric oxide（NO） were measured by biochemical analysis. Results： There was no significant difference in serum TC between control and treatment groups. Compared with the control＇ s, the effects of simvastatin were more significant in decreasing serum MDA level（P 〈 0.01 vs control＇ s at 2-week; P 〈 0.006 vs control＇ s at 4-week）, increasing serum SOD level（P 〈 0.03 vs control＇ s at 2-week; P 〈 0.003 vs control＇ s at 4-week） and NO level （P 〈 0.01 control＇ s at 2-week; P 〈 0.001 vs control＇ s at 4-week） either at 2 or 4 weeks. Conclusion： Simvastatin attenuates oxidative stress and protects endothelial function by the mechanisms of decreasing serum MDA level, increasing serum SOD level and NO level, which were inconsistent with its cholesterol-lowering effect. It may play an important role in primary（if not all） prevention of atherosclerosis and might be independent of lipid-regulation mechanism.展开更多
基金This study was supported by Provincial Natural Science Foundation of the Department of Education of Jiangsu(01 KJB320003)Innova-tion Fund of Nanjiing Medical University(CX 003001)
文摘Objective： To investigate the mechanisms that Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A（HMG-CoA） reductase inhibitor, plays an important role in primary prevention of atherosclerosis independently of its lipid-lowering effect in Apolipoprotein E-deficient mice in the early stage of atherosclerosis. Methods： Twenty-four 6-week old male apoE-deficient mice were randomly divided into two groups：control group（normal saline） and treatment group[simvastatin（5 mg/（kg · d））]. Simvastatin was administered to treatment group mice by gavage and the same volume of normal saline was administered to control group mice by the same method for 2 or 4 weeks. Total cholesterol（TC）, super-oxide dismutase（SOD）, malondialdehyde（MDA） and serum nitric oxide（NO） were measured by biochemical analysis. Results： There was no significant difference in serum TC between control and treatment groups. Compared with the control＇ s, the effects of simvastatin were more significant in decreasing serum MDA level（P 〈 0.01 vs control＇ s at 2-week; P 〈 0.006 vs control＇ s at 4-week）, increasing serum SOD level（P 〈 0.03 vs control＇ s at 2-week; P 〈 0.003 vs control＇ s at 4-week） and NO level （P 〈 0.01 control＇ s at 2-week; P 〈 0.001 vs control＇ s at 4-week） either at 2 or 4 weeks. Conclusion： Simvastatin attenuates oxidative stress and protects endothelial function by the mechanisms of decreasing serum MDA level, increasing serum SOD level and NO level, which were inconsistent with its cholesterol-lowering effect. It may play an important role in primary（if not all） prevention of atherosclerosis and might be independent of lipid-regulation mechanism.
