| Objectives: The diabetic macrovasculopathy is one of the most common chronic complications and the main cause attributed to the death and physical deformity in patients with T2DM, which remains the major concern of patients with diabetes. The risk of cardiovascular disease in such patients is two to four times higher than that of control patients. Atherosclerosis is the most important pathological change of diabetic macrovasculopathy. Although currently no directly implication in the development of diabetes-related atherosclerotic disease, NF-kB may serve as a primary initiator in diabetic vascular complications by promoting the expression of its target gene. In addition, growth factors and apoptosis related proteins have been implicated in the development of diabetic vascular complications in patients with diabetes. In this study, the animal model of diabetes mellitus induced by alloxan was used to study the relationship of diabetic atherosclerosis with NF-kB, endogenesis growth factors and apoptosis related proteins, and further to elucidate the pathogenesis of diabetic atherosclerosis.Methods: 24 Wistar rats were ramdomly divided into two groups: normal control group and diabetic group, each group had 12 rats. Diabetic rats was produced in experimental group by injection of 50 mg alloxan/kg BW via the tail vein. Control group was injected by 0.85% saline. Blood samples were taken from canthus veins for glucose test in the third day of injection. The glucose levels of all diabetic rats were more than>16.65mmol/L. After 10 weeks experimental term, the aorta samples were obtained and embedded in paraffin, 5μm sections were used to observe the general structure of the aorta tissue by HE staining and the expressions of NF-kB and VEGF , bFGF , bcl-2 , bax in aorta by immunohistochemistry.Results: After injection of alloxan, the rats became polydipsia, polyphagia, polyuria and weight loss, and while the serum glucose increased. Compared withcontrol group, the body weight was significantly decreased in diabetic group(.P<0.01), while the fasting glucose was significantly increased (PO.01). Underthe observation with microscope, there were no significant pathological changesin aortas of normal control rats. It was found that the thickness of topical tunicaintima of aortas increased in diabetic rats, which consisted of hyperplasic SMCs.But it was not found the typical pathological changes of AS such as the mass foamcells, etc. In each focus, the elastic lamina existed asymmetric thickness and somehad fissures and abruptions. The SMCs in superficial lamella showed slightproliferation and disorganized arrangement. Results of immunohistochemistry:Compared with control group, the expression of NF-kB was significantlyincreased in diabetic rats (PO.01), positive cell presented yellow in nucleus.There were the expression of NF-kB in both endothelial cells and smooth musclecells. The expression of bFGF was observed in aorta of diabetic rats, positive cellpresented yellow in cytoplasm. Compared with control group, the expression ofbFGF in diabetic group was significant increased (P<0.0l). The expression ofVEGF in diabetic group was significantly higher than control group (PO.01).Compared with control group, the expression of bcl-2 was decreased in aorta ofdiabetic rats, while the level of bax was increased (PO.01).Conclusions: After injection of alloxan, the rats became polydipsia, polyphagia, polyuria and weight decline, and while the serum glucose increased. Histological observation on aorta provided a proof to the early pathological changes of atherosclerosis causing by hyperglycemia. NF-kB was activated in aorta of diabetic rats and promoted the expression of its target genes of adhesion molecule, growth factors and apoptosis, then led to the occurrenc and development of diabetic atherosclerosis. Therefore, activated NF-kB might be a primary initiator of diabetic atherosclerosis. The levels of VEGF and bFGF in diabetic group were significantly higher than that in control group. VEGF and...
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