| Objective: To investigate the mechanism of vascalar system protective effect of rosiglitazone on diabetic rat carotid artery.Methods: Inbreeding, clean-48 male rats, weighing 180-220 g, were randomly divided into normal control group(A n = 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 performed peritoneal injection of streptozotocin (STZ) 50mg/kg and the rats in Group C were performed injection of 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. 3 days 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,fat and C-peptide. The carotid artery intima-media thickness(IMT) were measured , the morphology changes of the diabetic rat carotid artery were examined by light microscope and transmission electron microscope. The expression of phosphorylation IKK and phosphorylation IκBαwere determined by Immunohistochemistry .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 carotid artery IMT were increased markedly in GroupB and C(P<0.05). IMT of the rats in Group C was much lower than that in Group B.With the extension of the course, IMT of the rats in Group B was increased while the one in Group C reduced.The levels of TC,TG,LDL-C,HDL-C of group B were different significabtly than group A.3.Under light microscope, in Group B endothelial cells were spreaded disorderly.Smooth muscle cells were hyperplastic. The vessel wall of carotid artery is thicker and the lumens is incarcerated In Group C ,those pathological changes alleviated.4.Under electron microscope, compared with Group A, endothelial cells were degenerative and necrotic,and the elastic membrane was ruptured in Group B and C. There was no change in Group A. Compared with Group B , those changes significantly alleviated in Group C.5.Immunohistochemistry 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 carotid artery 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 IMT, and in group B the expression of phosphorylation IKK was positive correlation with the phosphorylation IκBαConclusion:1. The model of artherosclerosis rats was succeeding. The endothelial cells were spreaded disorderly.Smooth muscle cells were hyperplastic. The vessel wall of carotid artery is thicker and the lumens is incarcerated IMT of the rats was increased2. The result of linear correlations analyse showed:in group B the expression of phosphorylation IKK was positive correlation with the phosphorylation IκBα..With the development of diabetes ,the level of the expressions of phosphorylation IKK and phosphorylation IκBαwere risng .The results revealed that phosphorylation IKK and phosphorylation IκBαare the key factor of great vessel lesion of diabebetes mellitus.3. Rosiglitazone may play a protective role of the carotid artery by down-regulating IKK and IκBαand ultimately inhibiting NF-κB activation ,then reducing pathological damage of great vessel, alleviating the development of the artherosclerosis.
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