Effects of rosiglitazone and atorvastatin alone or combination on aortic atherosclerotic area and TNF-α in hypercholesterolemic rabbits

AIM:To investigate the effects of rosiglitazone and atorvastatin alone or combination on aortic atherosclerotic area and TNF-α synthesis in hypercholesterolemic rabbits. METHODS:Thirty male New Zealand rabbits were randomly divided into normal diet group(n=6) and high-cholesterol diet group(1% cholesterol diet, n=24). After 8 weeks, hypercholesterolemic rabbits were randomly fed with starch (starch group, n=6), atorvastatin(atorvastatin group, 5 mg·kg-1·d-1,n=6) or rosiglitazone (rosiglitazone group, 3 mg·kg-1·d-1,n=6), rosiglitazone plus atorvastatin [combination group, atorvastatin (5 mg·kg-1·d-1),rosiglitazone (3 mg·kg-1·d-1), n=6]. Four weeks later, all rabbits were killed, and monocytes were isolated from peripheral blood monocytes of these rabbits, then were cultured for 24 hours. TNF-α antigens in plasm and monocytes were measured by enzyme -linked immunosorbent assay. RESULTS: Compared with normal diet group, levels of TNF-α were increased in plasma and monocytes of high-cholesterol diet groups. Compared with starch group, the area of atherosclerotic lesions and the levels of TNF-α in plasma and monocytes of hypercholesterolemic rabbits were decreased in rosiglitazone ,atorvastatin, or rosiglitazone plus atorvastain groups, furthermore, which had a more significant reduction in rosiglitazone plus atorvastain group (P0.01). There was a positive correlation between the area of atherosclerotic lesions and the levels of TNF-α in plasm and monocytes (P0.01). CONCLUSION: Atorvastatin combined with rosiglitazone assuage atherosclerosis through suppressing TNF-α secretion in peripheral blood monocytes. Synergistic administration of rosiglitazone and atorvastatin exerts a better anti-atheromatous effect.