The Effect Of Oxidative Stress And PECAM-1 On The Aorta Of Diabetic Rats And The Intervention Study Of Probucol

Objectives To establish rat models of diabetes mellitus and to observe changes of he biomarkers of oxidative stress,SOD,MDA and 8-iso-PGF2αin serum and plasma,and the levels of platelet-endothelial cell adhesion molecule-1 in serum and expressed on the aorta, to discuss the effects of oxidative stress and PECAM-1 on the aorta in diabetes;and to explore the protective effects of probucol on the aorta in early stage.Methods fourty male healthy Wistar rats (180-220g) were randomly divided into two groups:normal control group C(n=8, fed with ordinary diet) and the model group M(n=32, fed with high-glucose and high-fat diet). Four weeks later, streptozotocin(STZ35mg/kg)was injected intraperitoneally to establish experimental diabetic rat models. Twenty-two rats became diabetes and randomly divided into two groups: (1) diabetes group (D group,n=11); (2) probucol treatment group (P group,n=11).After 8 weeks fed with high-glucose and high-fat diet, probucol treatment group were treated with Probucol(500mg/d.Kg) by daily intragastric administration for 8 weeks. At the end of the eighth week,the levels of blood glucose, serum concentration of HDL, LDL, TC, TG,SOD,MDA,8-iso-PGF2α,PECAM-1 were measured in each group,and the structure of aorta and the thickness of intima were observed by the light microscope;and the expression of PECAM-1 were assayed by Immunohistochemistry.Results (1) After high-glucose and high-fat diet for 4weeks and injection of STZ, the blood glucose and water consumption of the model group increased significantly (P<0.01), The level of body weight decreased significantly (P<0.01).(2) Compared with the normal control group,levels of TC, TG, LDL,MDA,8-iso-PGF2αin diabetes control group (D group) were significantly increased (P<0.01), SOD in the serum of D group were decreased than C group(P<0.01).(3) Compared with the normal control group, The level of PECAM-1 in D group was significantly increased(P<0.01), the expression of PECAM-1 in diabetes control group increased significantly (P<0.01).(4)Compared with the normal control group, the thickness of intima in the light microscope was increased(P<0.01),the morphology of aorta revealed that intima contained foam cells thickened, endothelial cells became swell and denaturation;the smooth cells were hyperplasia and irregular on tunica media.(5)Compared with the diabetes control group,the level of TC,LDL,MDA,8-iso-PGF2a in probucol treatment group(P group) decreased significantly(P<0.01), the level of SOD increased significantly (P<0.01), the level of PECAM-1 also decreased significantly(P<0.01), the thickness of intima in the light microscopehe and the expression of PECAM-1 in probucol treatment group decreased significantly (P<0.05).Conclusions(1) The level of oxidative stress in STZ-induced diabetic rats was increased;indicading that high blood glucose can cause oxidative stress.(2) The morphology of aorta showed that the intima of aorta in diabetic rats was thicked,indicading that high blood glucose and oxidatie stress can accelerate the progress of atherosclerosis in diabetic rats.(3) The level of PECAM-1 and the express of PECAM-1 in diabetic rats were increased,indicating that PECAM-1 may participate the progress of atherosclerosis.(4) The level of oxidative stress and the thickness of aorta intima were decreased,the level f PECAM-1 and the express of PECAM-1 in diabetic rats were decreased after the intervension of Probucol,indicating that anti-oxidant and down regulation the express of PECAM-1 may improve the aorta of diabetic rats.