| In recent years, diabetes has become a seriously diseases endangered the human life. It is confirmed that angina pectoris and myocardial infarction are frequent cardiovascular complications in diabetic patients. The mortality of myocardial infarction in patients with diabetes was 3-4 times higher than those without it. In addition, heart failure and re-infarction are increased in the myocardial infarction patients combined with diabetes significantly. Therefore, the treatment of diabetes should not only be based on lowering blood glucose and, more importantly, to improve the diabetic metabolic disorder and reduce cardiovascular and cerebrovascular complications.Rosiglitazone, a hypoglycemic agent of thiazolidinediones (TZDs), has attracted remarkable scientific interest on novel and potent improveing insulin- sensitizing agents, and to lighten insulin resistance, more over, to correct metabolic disturbance. Patients with type 2 diabetes are at a high risk for cardio- vascular disease,resulting in increased mortality rates. So there is an urgent need to develop a hypoglycemic agent with protective effects on the cardiova- scular system. In this topic, we will research the protective effects of Rosiglitazone on acute myocardial I/R injure in normal and Type 2 diabetic (T2DM) rats.Rosiglitazone is a specific agonist of PPARγ. PPARγis an important factor for regulating body metabolism, in particular metabolism of fatty acid and glucose. It can promote adipocyte differentiation; increase the expression of fatty acid transport protein and fatty acid transporter enzyme. It also could stimulate fatty acids be intake and transformation, and enhance insulin-responsive and glucose uptake by adjusting the expression of downstream gene, thereby improve the energy metabolism of myocardial significantly. Therefore, we proposed to investigate the mechanism of rosiglitazone on the perspective of energy metabolism of myocardial.Methods:1.The effects of rosiglitazone on myocardial ischemia-reperfusion ( I/R) in normal rats: I/R injury rat model was induced via ligating left anterior descending branch of coronary artery for 30 min and reperfusing for 120 min; Rats were randomly divided into rosiglitazone, I/R and shame- operated group. Myocardial infarct size (IS) and the ratio of IS and area at risk (AAR) were determined, arrhythmias score was evaluated according to Lambeth conventions, and blood pressure (BP) was recorded 1 w after intragastric administration and I/R injury operation. The ultrastr- ucture of cadiocyte was observed by electron microscope.2.The effects of rosiglitazone on myocardial ischemia-reperfusion (I-R) in T2DM rats: T2DM ratmodelwas established by high lipid diet combined multiple low dose strep tozocin (STZ); T2DM rats were randomly divided into rosiglitazone, I/R and shame-operated groups.3. Myocardial protein was extracted in each group. The protein level of PPARγ,PGC1,UCP2 and UCP3 in cardiac muscle was measured using western blot. Actin,a conservative protein,was used as an interner control to adjust the concentration of each sample.Results:1. The effects of rosiglitazone on I/R in normal rats: Compared with IR group, rosiglitazone decreased the ration of IS/LV (29.3±4.9vs 37.6±3.2) and the rate of AAR /LV (76.1±9.6 vs 93.5±7.4), reduced scores of arrhythmias (2.6±0.4 vs 4.2±0.6) and ameliorated the restore of BP in reperfusion period (P < 0.05).2. The effects of rosiglitazone on I/R in T2DM rats: Compared with IR group, rosiglitazone decreased the ration of IS/LV (30.3±3.6 vs 38.7±3.0) and the rate of AAR /LV (76.0±2.6 vs 93.2±3.0) , reduced scores of arrhythmias (2.6±0.4 vs 4.4±0.8) and ameliorated the restore of BP in reperfusion period (P < 0.05).3. Compared with control group, PPARγ,PGC1,UCP2 and UCP3 are increased in the cardiac musculature. It is suggested that in diabetes, due to elevated blood sugar and abnormal glucose metabolism, there have been some changes on energy metabolism of myocardial and myocardial fatty acid oxidation may be enhance compensatory. However, the protein level of PPARγand PGC-1 decreased in DM-I-R group, with UCP2 sharply raised up. The UCP3 was also up-regulated in I-R group, compared with DM group. It shows that when myocardial ischemia was developed in diabetic rats, fatty acid dysoxidation was happen, combined with a serious shortage of oxygen supply, myocardial energy supply was insufficient; At the same time UCP2, UCP3 were over-expression, which made the oxidative phosphorylation uncoupling. Thereby it prevented ATP synthesis, and enhanced energy deficiency, manifested as myocardial energy depletion; And RSG can noteably swtch these changes, compared with I-R group.Conclusions:Rosiglitazone has the protective effects on acute myocardial I/R injure in normal and T2DM rats and it may be associated with the improvment of energy metabolism of cadiocyte.
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