Effects of simvastatin on early oxidative stress and endothelial function in apolipoprotein E-deficient mice

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 bio-chemical 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.