| Objective:To investigate the mechanism of heart protective effect of rosiglitazone on diabetic rat heart.Methods:48 clean close breeding male rats were randomly divided into normal control group(An=16),diabetic rat group(B n=16) and rosiglitazone treatment group(C n=16).After 12 hours fast,the rats in Group B and C were disposable performed peritoneal injection of streptozotocin(STZ) 50mg/kg and the rats in Group C were performed injection of 0.1mol/L citric acid buffer with the equal volume.72 hours later,the rats in Group B and C whose blood glucose was above 16.7mmol/L three consecutive days were identified as modeling success,whereas those in Group B and C whose blood glucose was less than 16.7mmol/L were excluded.1 weeks later,rosiglitazone was taken for therapeutic intervention(5 mg / kg body weight everyday) in group C,while the ones in groups A and B were taken with the similar does of isotonic Na chloride.We randomly killed eight rats of every group respectively at the eighth and twelfth week.The weight of every subject was measured.The blood samples were obtained to measure the levels of blood glucose,C-peptide.The index of myocardial weight and area of myocardial cells were measured at the same time.Immunohistochemistry were used to examine the expression of phosphorylation IKK and phosphorylation IκBαin the heart of STZ diabetic rats.The cardiac muscle was fixed and embedded,the pathological changes of cardiac muscle were examined using light microscope and electron microscope.Results:1.After 72 hours of STZ injection,compared with Group A,blood glucose in Group B and C was significantly higher(P＜0.05).Fasting C-peptide in Group B and C was significantly lower than that in Group A(P＜0.05).In comparison with Group A,the body weight in Group B were decreased(P＜0.05).Compared with Group B,the body weight in Group C were increased (P＜0.05).2.At 8,12 weeks,compared with Group A,the index of myocardial weight,area of myocardial cell were increased markedly in GroupB and C(P＜0.05).The index of Group C were much lower than Group B(P＜0.05).With the extension of the course,the index of the rats in Group B was increased while the one in Group C reduced(P＜0.05).3.Under light microscope,compared with Group A,in Group B,Myocardial hypertrophy, rarefactioned,myofibrils fragmentation at 8 weeks.Extracellular matrix increased,fibration markedly at 12 weeks.With the extension of the course,the pathological changes of the rats in Group B was increased while the one in Group C reduced.4.Under electron microscope,compared with Group A,myocardial mitochondrion were swelled and degenerationed,myofibril were focally dissolved degeneration myocardial fibers arranged irregularly,and fractured in group B and C;pathological changes were aggravated in group B,myocardial pathological changes were alleviated in group C,while reduced obviously along with the treatment course progress.5.Immunohistochernistry of semi-quantitative analysis showed that the rats in Group A had a small amount of phosphorylation IKK and phosphorylation IκBαexpression.At 8,12 weeks, phosphorylation IKK and phosphorylation IκBαexpression in the myocardial cell of Group B and C were higher than those of Group A.Compared with Group B,the expression of phosphorylation IKK and phosphorylation IκBαin Group C was significantly lower,and there was a downward trend with the extension of the course.The result of linear correlations analyse showed:in group B the expression of phosphorylation IKK and phosphorylation IκBαwere positive correlation with the index of myocardial weight and area of myocardial cells,and in group B the expression of phosphorylation IKK was positive correlation with the phosphorylation IκBα(P＜0.01).Conclusions:Rosiglitazone could significantly reduce the expression of Phosphorylation IKK and Phosphorylation IκBαin streptozocin-induced diabetic rats.Rosiglitazone could decrease the index of myocardial weight and area of myocardial cells,to play a protective role in Diabetic Cardiomyopathy.The mechanism of heart protective effect might be linking with PPAR_γ,inhibiting IKK phosphorylation,then inhibiting IκB degradation,ultimately prohibiting NF-κB activation,reducing the myocardial pathological damage,attaining to protection of myocardium.
|
PDF Full Text Request