The Effect Of Ages On Aortic Structure And Function In Diabetic Rats And Discussion Of The Mechanism

Background and ObjectiveDiabetes mellitus (DM) is a kind of general disease, and pathological changes in blood vessels is one of its major complications. Former studies suggested that non-enzymatic glycation happened commonly, and immoderate non-enzymatic glycation and accumulation of advanced glycation end products (AGEs) had an extensive injury to the structure of body tissue, especially to the large vessels. In the recent years, with the increasing effort given to the study of vasculopathy caused by AGEs, people have had a deeper insight into the area.This experiment aims to observe and explore the action of AGEs and the protective effect of aminoguanidine (AG) and Valsartan(VT )on the vascular structure and function in diabetic rats which were induced by diet and streptozotocin (STZ).The study includes the following: the establishment of diabetic rat model and model detection; observation of the depositive condition of AGEs in aortic endothelium in rats of different experimental group; evaluation of the effect of AGEs, AG and VT on systolic and diastolic function in aortas; detection of the effect of AGEs , AG and VT on ultrastructure of endothelium in aortas of the rats.MethodsEstablishing diabetic rat model and model detection; AG and VT were used as intervention factors; immunohistochemistry and ELISA were used to assay the depositive condition of AGEs in aortic endothelium in rats of different experimental group; aortic ring experiment was used to evaluate the vasomotorial function, and electron microscopy was used to detect the ultrastructural changes of endothelium in aortas of diabetic rats; Western blot analysis was used to detect the expression of endothelial nitric oxide synthase (eNOS).Results1. Immunohistochemistry and ELISA results showed that the content of AGEs in aortas of diabetic rats was increased, and most AGEs presented in the aortic endothelium; treatment with AG could reduce the formation of AGEs while treatment with VT could not.2. The results of vasomotorial function of isolated aortic ring suggested that the contractile response to NA in diabetic rats was significantly enhanced, while the vasodilator response to ACh was significantly decreased. The results also demonstrated that following the treatment of AG or VT to diabetic rats could reduce the changes above, that is, reducing the vascular sensitivity to the NA and increasing the vascular sensitivity to ACh.3. The results of aortic ultrastructure demonstrated that pathologic changes appeared in aortic endothelial ultrastructure in diabetic rats, and compared with the diabetic rats , aortic endothelial ultrastructure was improved in diabetic rats which had received AG or VT treatment. 4. The results of Western blot analysis showed that the expression of endothelial nitric oxide synthase (eNOS) in diabetic rats was significantly decreased and with treatment of AG or VT, expression of eNOS was increased. ConclusionsAGEs appears to be more abundant in aortas in diabetic rats and it damages the aortic structure and function. AG could prevent the accumulation of AGEs while VT could not. But both of them might have a protective effect on the structure and function in aorta.