The Effectof Rosiglitazone On Inflammation,Oxidative Stress And Atrial Remodeling In Diabetic Rabitts

Objective Atrial Fibrillation (AF) is one of the most common arrhythmia. Atrial remodeling promote the occurrence or maintenance of AF by acting on the fundamental arrhythmia mechanisms. Inflammation and oxidative stress play an important role in the pathogenesis of atrial remodeling. Due to Rosiglitazone’s anti-inflammatory properties, it might exert beneficial effects on atrial remodeling. In the present study, we investigated the underlying mechanisms for the effect caused by rosiglitazone on atrial structural remodeling and electrical remodeling in alloxan-induced diabete rabbits, at observations and the cellular and molecular level. The focus is role of inflammation and oxidative stress, atrial fibrosis in AF.Methods30rabbits were randomly divided into three groups:normal control group (C group), diabetic group (D group) and diabetic rosiglitazone treatment group (DR group).20of30rabbits were used to established alloxan-induced diabete models by injection of alloxan by ear vein. After the modeling, were randomly divided into two groups,10rabbits each group, were fed around in the same environment for4weeks. In DR group each rabbit received additionally4mg/day rosiglitazone. Every week each rabbit body weight and fasting blood glucose was measured, and baseline levels of markers of inflammation and oxidative stress in rabbits and insulin levels were measured too.4weeks later venous blood was taken from the rabbit ear vein for determination of levels of all above makers. Then isolated Langendorff-perfused rabbit hearts were made, electrophysiological parameters were mesured untill atrial fibrillation was induced. Finally, the left atrial tissues of left were fixed in formalin for pathological examination of myocardial fibrosis. All measured data are analyaed by appropriate statistical methods.Results (A) Compared with the control group, TNF-a and hs-CRP of the diabetic group were statistically significantly higher (p<0.05). Inflammatory markers of the rosiglitazone group were statistically significantly lower those of the diabetic group (p<0.05), while similar level with the control group (p>0.05).(B) Of the Diabetes Group SOD activity was statistically significantly lower than that in the control group (p<0.05), while MDA level was statistically significantly higher (p<0.05). In the rosiglitazone group and the control group, there was no significantly significant difference between SOD and MDA levels (p>0.05). SOD activity of the diabetic group was significantly lower than that of the rosiglitazone group, but MDA levels were significantly higher (p<0.05). No significant differences of GSH and NO and02and NOS levels were there among the three groups (p>0.05).(C)(1) Compared with the control group, basic cycle length in sinus rhythm and heart conduction time of the diabetic group was significantly longer (p<0.05), of the rosiglitazone group sinus cycle longer, but the heart conduction time is no significantly longer (p>0.05).(2) Atrioventricular conduction time was not significantly different between in the diabetic group and the rosiglitazone group (p<0.05), but in both was longer than the control group (P<0.05).(3) No significant difference between in the diabetic group and the rosiglitazone group was found, but in both was shorter than in the control group (P<0.05).(4) Atrial fibrillation could not be induced in the control group, in the diabetes group and the rosiglitazone group,5and3rabbit hearts atrial fibrillation could be induced respectively, The number of induced occurrences in the diabetes group was15times, while in the rosiglitazone group was5times. The episode of atrial fibrillation in the rosiglitazone group was significantly shorter than in the diabetic group.(D) Histopathological examination revealed that in the diabetic group, left atrial cardiomyocytes disordered accompanied by inflammatory cell infiltration. In rosiglitazone group significantly pathological changes reduced. MASSON staining showed that in left atrium in the diabetic group interstitial collagen volume fraction increased significantly (p<0.05), and in rosiglitazone group, collagen volume fraction significantly reduced, with significantly differences between two groups (p<0.05).Conclusions Rosiglitazone has certain antagonist activity on inflammation and oxidative stress and improve atrial fibrosis in diabetes rabbits, which resulting in reversal effect on atrial structural remodeling and electrical remodeling. Rosiglitazone may play some degree of prevention from atrial fibrillation in diabetes.