Study on the role of oxidative stress in the kidneys of diabetic rats / 中国病理生理杂志

ABSTRACT

AIM: To investigate the changes of oxidative stress in the kidneys and their roles in nephropathy in diabetic rats. METHODS: Diabetic rats were induced by streptozotocin (STZ). 36 rats were divided into three groups randomly (1) NC group, normal control rats; (2) DM group, diabetic rats received protamine zinc insulin (PZI) 2U-4U/2 d; (3) DT group, diabetic rats received PZI 9-12 U/kg body weigh/day. 12 weeks later, rats were killed, blood glucose, blood cholesterol, serum creatinine, blood urea nitrogen, HbA1c, urinary creatinine, and urinary protein for 24 h were measured. The activities of antioxidant enzymes in renal cortex, including total superoxide dismutase (TSOD), Cu-Zn superoxide dismutase (Cu-Zn SOD), Mn superoxide dismutase (Mn SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and maleic dialdehyde (MDA) were measured by chromatometry. RT-PCR was performed to detect the expression of different antioxidant enzymes mRNA. RESULTS: For all the targets we measured, there was no significant difference between NC and DT groups. Compared with the other two groups, the levels of blood glucose, cholesterol, trigalloyl glycerol, HbA1c in DM group increased significantly. The activities of TSOD, Cu-Zn SOD and CAT decreased significantly. The activity of GSH-Px increased significantly. There was no significant difference among the activities of Mn SOD in all three groups. The level of MDA in DM group was much higher than that in NC or DT group. The relative expression levels of GSH-Px and Cu-Zn SOD mRNA in DM group were higher than those in other two groups, while the relative expression level of CAT decreased. Mn SOD mRNA was expressed without significant difference in all groups. Compared with NC or DT group, urinary protein in DM group increased significantly, while creatinine clearance rate decreased. CONCLUSIONS: Hyperglycemia affected the expression of antioxidant enzymes. Oxidative stress was caused by hyperglycemia in diabetic rats and may be an important factor in the etiology of diabetic nephropathy.