Effects Of Probucol On Oxidative Stress And Pancreatic Islets Function In Type 2 Diabetic Rats

Objective: To establish the animal model of type 2 diabetes mellitus and to observe the levels of nitrotyrosine and 8-hydroxy-2'-deoxyguanosine, which were the biomarkers of oxidative stress. And to observe the effects on oxidative stress and pancreatic islets function in diabetic rats by treated with probucol in early stage.Methods: The male Wister rats of 8 weeks old randomly devided into C (n=7),D (n=9) and P (n=7). C was the normal control group, feeding with regular diets ,4 weeks later injected citrate buffer liquid in abdominal cavity; D was the type 2 dibetes model group, feeding with the diets enriched with high-fat and high-sucrose, 4 weeks later injected the aqua of streptozotocin(STZ) at a dose of 30mg/Kg body weight in abdominal cavity; P was the probucol group, feeding with the diets enriched with high-lipid,high-sucrose and probucol, 4 weeks later injected the aqua of streptozotocin(STZ) at a dose of 30mg/Kg body weight. 10 weeks later, measured the fasting plasma glucose(FPG), fasting insuline(FINS), total cholesterol(TC), triglyceride(TG),MDA and SOD,and calculated the insulin sensitivity index(ISI). To observe the expression of NT,8-OHdG and insulin by immunohistochemistric method.Results: The FPG,TG,TC and MDA level of C and D group were significantly increased(P<0.01), and the average optical density of NT and 8-OHdG were much higher than C group(P<0.01), but the markers of P group decreased significantly to compared with D group(P<0.01). The level of SOD, value of ISI and percentage of the insulin positive area in the pancreatic islets of D and P group were much lower than C group(P<0.01), however, the markers of P group were higher than D group apparently(P<0.01). The FINS level of C and P group had no significant difference, whereas they increased significantly to compared with D group. Conclusions: The activities of oxidative stress were enhanced and function of pancreatic islets degenerated apparently in diabetes condition. With the treatment of probucol in early stage, the levels of TG and TC decreased significantly, meanwhile partially reduced the FPG and restored the pancreatic islets function acting through as an antioxidant. This suggests that oxidative stress may play an important role in the mechanism of type 2 diabetes mellitus.