Effect of irbesartan on activation of renal nuclear factor-kappa B in experimental type 2 diabetic rat

Objective To develop a rat model of type 2 diabetes, and to investigate the effect of AT1 receptor antagonist-irbesartan on activation of renal NF-κB in type 2 diabetic rat. Methods The rats of model groups were intraperitoneally given low-dose streptozotocin (STZ, 30 mg/kg) after having the sucrose-and fat-enriched diets(20% sucrose, 10% pig fat, 2. 5% cholesterol) for one month. Immuohistochemistry and computer image-pattern analysis system were used to analyze activation of NF-κB and expression of monocyte/macrophage (ED-1) in renal tissues. Results (1) Insulin resistance was induced by feeding diets enriched in sucrose and fat, and hyperglycemia was induced with a dose of STZ that did not cause diabetes in chow-fed rats. After 6 weeks, rats of model group presented itself early changes of diabetic nephropathy (DN). (2) Compared to normal group, the activation of NF-κB and expression of ED-1 increased in glomeruli of experimental type 2 diabetic rat. Irbesartan inhibited significantly the activation of NF-κB, ameliorated monocyte/macrophage infiltration, partly improved the renal function and matrix accumulation. Conclusions (1) A rat model of type 2 diabetes mellitus is developed successfully by combination of dietary-induced insulin resistance and low-dose STZ-induced hyperglycemia. (2) Renal NF-κB activation is greatly increased in experimental type 2 diabetic rat. The protection of irbesartan against kidney is associated, at least in part, with down-regulating NF-κB activation and monocyte/macrophage recruitment in renal tissue.