Effects Of Rosiglitazone On The Oxidative Stress And Atheorscleorsis In Diabetes Rabbits

0bjective To evaluat the effets of different phase of rosiglitazone on the progression of aortic atheorsclerotic plaque in New Zealand rabbits ,which were fed with cholesterol rich diet and injected CTX. To reveal the effets of rosiglitazone on the oxidative markers and the content of NADPH oxidase in the different phase of atheorsclerotic plaque,investigating the possible mechanism of rosiglitazone on the progression of atheorsclerotic plaque.Methods Thirty eight New Zeal white rabbits were fed on cholesterol rich diet and injected with CTX for the diabetic and atheorsclerotic models.The rabbits were administered with rosiglitazone at prevention group (n=8),treatment group(n=8) and distlled water(n=9) by gastric gavage once a day for 12 weeks.Normal diet group(n=8) were also randomly selected .After measurement of the serum glucose ,the serum lipids,the serum insulin,the rabbits aortas were fixed and pathologically analyzed, to measure plaquesize, plaque/intima size ratio ,intima/medium thickness ratio. The expression of NADPH oxidase p22phox,gp91phox were detected by quantitative real-time PCR. At the same time the expression of NADPH oxidase p22phox, gp91phox in the plaque were dectected by immuohistochemistry. The MDA content of serum, the SOD activity and the total resistance to oxidation were also detected.Results The three high-cholesterol diet groups were significant artherosclerotic plaque, compared with the normal diet group.In comparision with model group ,the intima/medium thickness ratio, plaquesize, plaque/intima size ratio were significantly decreased(P<0.05) in the rosiglitazone treatment group and the rosiglitazone prevention group;the changes in the rosiglitazone prevention group were the most.The parameters of the serum lipids,the serum glucose,the serum insulin ,MDA, NADPH oxidase p22phox,gp91phox mRNA were significant increased(P<0.05) in the model group compared with the normal diet group.All the parameters except for the SOD activity and the total resistance to oxidation were decreased in groups administered with rosiglitazone (P<0.05) in a time-dependent manner.Conclusion It was proved that the preparation of the animal modek of diabitic atherosclerosis was successful. Free radical injury induced by oxidative modification is one of the important mechanisms of the pathogenesis of atherosclerosis,which is manifested by increase in the serum glucose ,the serum lipids,the serum insulin, the intima/medium thickness ratio, plaquesize, NADPH oxidase p22phox,gp91phox, manifested by decrease the SOD activity and the total resistance to oxidation.In some extent rosiglitazone improved all the levels ,reduced the impaires resulted from free radicals and regulated the effects of protection of antioxidation in vivo.