Rosuvastatin And Pioglitazone In Diabetic Rats With Early Atherosclerosis Formation

Objective:Observe the role of selective HMG-CoA reductase inhibitor Rosuvastatin joint peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist Pioglitazone in diabetic rats with early formation of atherosclerosis and explore its relevant mechanisms.Method:Fifty Wister rats were randomly divided into five groups:normal control group (NC), diabetic (DM) group, rosuvastatin (Rosu) group, pioglitazone (Piog) group, rosuvastatin combined pioglitazone group (R&P),10rats in each group. High fat and high glucose diet were used to establish a DM rat model. DM group, Rosu group, Piog group, R&P group were given high-sugar high-fat diet and then given intraperitoneal injection of50mg/kg streptozotocin after4weeks; NC group were offerred full diet and given citrate buffer as control. On this basis, Rosu,5mg/(kg· d), for Rosu group; Piog5mg/(kg· d) for Piog group; Rosu5mg/(kg· d) and Piog5mg/(kg· d) for R&P group, and normal saline for NC group, all the medicine were given through intragastric administration for above four groups. TC, TG, LDL-C and BG were measured. Immunohistochemistry was used to analyze the expressions of matrix metalloproteinase-9(MMP-9) and PPAR-γ receptors and mononuclear cell infiltration.Result:The levels of TC, TG, LDL-C and BG in DM, Rosu group, Piog group, R&P group were markedly higher than that of NC(F=66.89～273.24,q=3.93-46.60, P<0.05), but lower than that of DM (q=1.82-26.02, P<0.05), the differences of the levels of LDL-c between R&P group and Rosu and Piog groups were significant (q=3,93-29.85, P<0.05); while the MMP-9, PPARy expression and infiltration of mononuclear cells in DM, Rosu group, Piog group, R&P group were markedly higher than that of NC (F=29.39～593.33,#=5.03-59.62, P<0.05), but lower than that of DM(q=3.14-54.89, P<0.05). the differences of the levels of MMP-9, PPARy expression and infiltration of mononuclear cells between R&P group and Rosu and Piog groups were significant (q=2.85-24.72, P<0.05)Conclusion:Rosuvastatin can reduce TC, TG, LDL-C, MMP-9and PPAR-γ of rats expression; pioglitazone can reduce the LDL-C and BG, decreasing MMP-9and PPAR-y expression. Rosuvastatin combined pioglitazone applications can be more effective in reducing the concentration of LDL-C and inhibiting MMP-9and PPAR-γ expression and menonuclear cell infiltration, to prevent the formation of diabetic rats with early atherosclerosis.