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Protection of Melatonin on Myocardium and Aortic Endothelial Cells of Diabetic Rats

BackgroudNow diabetes has been the third disease secondary to vascular diseases and cancer which endanger human health seriously, and chronic complications of diabetes are the maincauses which decrease life quality and result in disables and death of the diabetics. Cardiac and vascular pathology are the common diabetic complications. Compared with non-diabetics, the diabetics have 2-3 times the morbidity of cardiovascular diseases, and are of more serious degree.The mechanism of complication of diabetes with atherosclerosis is related to increase of free radical production and decrease of antioxidant status in the body. In addition, endothelial abnormities of diabetes are also related to oxidant stress and the formation of advanced glycation end products (AGEs). Endothelial abnormities result in artery stricture prone to deposition of patches. Diabetic myocardiopathy results from microvascular and myocardium abnormities through complicated mechanism. Many epidemic and clinical researches indicate that there are close relation between superoxidance and diabetic cardiovascular complications, which have attracted much attention.The control of blood glucose, lipid and other hazard factors are the main therapy of diabetic chronic complications nowadays. However, United Kingdom Prosperous Diabetic Studies(UKPDS) did not draw the conclusion that intensive treatment can dicrease the hazard of macrovascular complications. It is known that diabetes and its chronic complications are related to oxidant stress. The prevention and cure of antioxidant therapy have been studied extensively. It has been reported and antioxidant such as Vitamin E ameliorated diabetic cardiovascular diseases.Melatonin is the strongest free radical scavenger which can prevent the injury of free radicals by cleaning out free radicals directly and enhancing the activities of antioxidases. The results of animal experiments proved that melatonin prevented the pancrease damage bystreptozotocin, prevented and cured ischemic and reperfusion injury of heart, and ameliorate adriamycin-induced cardiomyopathy, etc. But the protection of melatonin on diabetic cardiovascular diseases has not been reported yet.Therefore, we treated diabetic rats induced by streptozotocin with melatonin for 8 weeks to observe its antioxidant effects and its protection of myocardial tissues; Secondly, we cultivated bovine aorta endothelial cells in vitro and assay diastol ic agents to observe the protective effects on artery endothelial cells.Methods1. The effects of melatonin on myocardium of diabetic rats (1) Diabetic rats were induced by streptozotocin and treated with different doses of melatonin for 8 weeks. Body weight, blood glucose, triglyceride and cholesterin were measured.(2) After being treated with melatonin for 8 weeks, peripheral blood and myocardial tissues of rats were assayed with total antioxidant capacity, malondialdehyde and glutathione peroxidase.(3) After being treated with melatonin for 8 weeks, pathological changes under photics microscope and electron microscope were observed.(4) After being treated with melatonin for 8 weeks, the myocardial expression of TGF-B1 and TGF-B1 mRNA of rats were identified.2. The effects of melatonin on aorta endothelial cells of diabetic rats Bovine aorta endothelial cells were cultivated in vitro and incubataed with different concentration of melatonin and glucose. The concentration of prostacyclin and nitric oxidase activity in the midium and inducible nitric oxidase mRNA expression of endothelial cells were identified.Results1. Melatonin had no effects on body weight, blood glucose, cholesterin of diabetic rats, but it decreased triglyceride level.2. Melatonin had no effects on serum total antioxidant capacities of diabetic rats.3. High doses of melatonin decreased serum MDA level of diabetic rats. Either highdoses or low doses of melatonin decreased MDA level in myocardium of diabetic rats.4. High doses of melatonin increased serum GSH

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