Protection Of Melatonin On Aortic Endothelium And Islet Cell Of Insulin Resistance Rats

With the development of economics, people' s life style has changed greatly, the prevalence rate of diabetes as well as heart and brain vascular disease has rised rapidly. Among the disease which endanger human health severely, heart and brain vascular disease lists the first and disease lists the third. Insulin resistance as the important virulence factor involve in the pathogenesis of both diabetes and heart or brain vascular disease. Now the researchers in diabetes and heart or brain vascular disease field pay close attension to the pathogenesis of insulin resistance and the treat treasures aim to the pathogenesis of insulin resistance .In the research of pathogenesis of insulin resistance , there are different viewpoints about the sequence of the insulin resistance and islet B cells damage. At present , whther insulin resistance secondary to islet B cells damage or islet B cells damage secondary to insulin resistance is not very clear. The vascular endothelial dysfunction of insulin targeting tissues including skeletal muscles, liver and adipose is a key findings. Nevertheless, the structure and functional state of some important organs excluding insulin targeting tissues e.g. aorta, myocardium, renal cortex in the process of insulin resistance occurrence has not been reported systeraicly. Melatonin is the strongest free radical scavenger which can prevent the injury of free radicals by cleaning out free radicals directly and enhance the activities of antioxidases. Melatonin also can defenses effectively lipid peroxidation injury, therefore has broad spectrumanti-free-radicals damage roles. Melatonin has comprehensive biology actions for Melatonin receptor (MR) expresses at many tissues and organs. But, the role of Melatonin on the endothelium of aorta, myocardium, renal cortex as well as islet P cell in insulin resistance has not been reported. So, we reproduced insulin-resistant rats model from 6-8 weeks age Sprague-Dawwley(SD) rats by high-glucose diet ( 70% calories from glucose )to observe the ultrastructure of aorta endothelium and islet P cells as well as the expression of endothelin-1 and endothelial nitric oxide synthase in early insulin resistance state. Moreover,we researched the role of melatonin to aorta, myocardium, renal cortex and islet P cells and compared with rosiglitazone. In this study, we wanted to elucidate the following questions as for the insulin-resistant rats model: (1). Does the damage of islet P cells occur at the same time with insulin resistance or as the result of insulin resistance and secondary to it's metabolism disorder? (2). When vascular endothelium dysfuntion of insulin targeting tissues occurs,dose the vascular endothelium structural and functional abnormality also occur at the same time? (3). Dose melatonin have protectactive role on aorta, myocardium, renal cortex and islet P cells?Methods1. Insulin-resistant rats were reproduced from 6-8 weeks age Sprague-Dawwley rats by high-glucose diet. Experiment rats were divided four groups: normal control(CN);insulin resistance(IR); melatonin(Mel); ros i gli tazone(RSG).2. The body weight,systolic blood pressure, fasting blood glucose(FBG), postprandial blood glucose serum triglyceride, free fatty acid, insulin, ,high-density lipoprotein, low-density lipoprotein(LDL-c), malondialdehyde, superoxide dismutese were assayed and insulin sensitivityindex was calculated in all groups.3. Ultrastructure Of aorta endothelium and isletPcells was observed with transmission electron microscopes in all groups.4. The protein expression of endothelin-1 ande endothelial nitric oxide synthase was measured by demi-quantify immunohistochemistry.5. The mRNA expression of endothelin-1 ande endothelial nitric oxide synthase was measured by demi-quantify Reverse transcriptive polymerase chian reaction.Results1. After 6 weeks, Systolic blood pressure(SBP) and serum triglyceride(TG) rised and insulin sensitivity index(ISI) reduced in high-glucose diet induced rats. Fasting blood glucose (FBG)and postprand...