Abstract:

Objective To study the effects of protein kinase C(PKC)-β inhibitor LY333531 on nicotinamide dinucleotide phosphate(NADPH) oxidase and superoxide dismutase(SOD) in diabetic kidney.
Methods Twenty-four male SD rats were randomly assigned to control group, diabetic group and diabetic with LY333531〔1 mg/(kg·d)〕 treatment group. After the treatment with LY333531 for four weeks, the levels of blood glucose, kidney weight/body weight, 24-hour urinary albumin, creatinine clearance rate(Ccr), free 15-F2t-Isoprostane, total antioxidant concentration and SOD activity were measured. The subunits P22phox and P67phox of NADPH oxidase, Cu/Zn-SOD and Mn-SOD protein expression were analyzed by Western blotting.
Results The levels of blood glucose, kidney weight/body weight, 24-hour urinary albumin, creatinine clearance rate, 15-F2t-Isoprostane in plasma and kidney, total antioxidant concentrations in plasma, the protein expression of P22phox and P67phox were all increased, but the levels of total antioxidant concentrations in kidney, SOD activity in plasma and kidney, Cu/Zn-SOD and Mn-SOD protein expression were significantly decreased in diabetic group as compared with control group(P<0.05). The treatment with LY333531 significantly prevented all these changes except for blood glucose and MnSOD protein expression.
Conclusion The PKC-β inhibitor LY333531 may protect early diabetic kidney from oxidative injury by inhibiting NADPH oxidase activation and expression, and restoring SOD activity by improving the expression of Cu/Zn-SOD subunit.

Key words: protein kinase C-&beta, inhibitor;LY333531;diabetic nephropathy;nicotinamide dinucleotide phosphate oxidase;superoxide dismutase