The Effect of Rosiglitazone and Simvastatin on Atherosclerosis in Cholesterol-fed Rabbits

Objective To study the effect of Rosiglitazone and Simvastatin on atherosclerosis and potential mechalism in rabbits. Methods 40 healthy Japanese big-ear rabbits were randomly divided into five groups with 8 rabbits in each group. Normal control group was fed with common forage for 11 weeks.Model group was fed with fat forage (common forage contained 1% cholesterol and 8% lard). Rosiglitazone group was fed with fat forage and rosglitazone 0.5·kg-1·d-1. Simvastatin group was fed with fat forage and samvastatin 2.5·kg-1·d-1. Rosiglitazone and Simvastatin groups were fed with fat forage and rosglitazone 0.5·kg-1·d-1.and samvastatin 2.5·kg-1·d-1. At the end of the experiment,blood samples of the rabbits were collected for biochemistry analysis and aorta was prepared for morphologic analysis. Results Compared with the control group,the levels of serum TC,TG,LDL-C,CRP,ET-1 and ADMA in model group increased obviously and the levels of NO and HDL-C decreased(P0.01). The levels of serum CRP,ET-1 in the treatment groups were significantly lower and the levels of NO were higher than those of normal group(P0.01). Compared with those in model group,the levels of serum ADMA in haplo-Rosiglitazone group or in the combination group significantly decreased(P0.01). The levels of TC,TG and LDL-C in haplo-Simvastation group or in the combination group were significantly lower than those of the model group(P0.01).The atheromatous plaques area and intima-to-media in model group were obviously higher than those of the normal group(P0.01). The combinationgroup significantly reduced the extent of atherosclerosis of longitudinal section.Conclusion Rosiglitazone and Samvastatin can prevent the development of atherosclerosis through inhibitting the inflammatory reaction,effect. protecting endothelial function and regulatting lipid metabolism. They have synergetic effect.