FK506 ameliorates renal injury in early experimental diabetic rats induced by streptozotocin

Abstract

Calcineurin (CaN) plays an important role in glomerular hypertrophy and extracellular matrix accumulation in early diabetic nephropathy. Cyclosporine (CSA), a CaN inhibitor, has been shown to reduce renal injury in streptozotocin-induced diabetic rats. We examined whether FK506, which immunosuppressive action was 10-100 times of CSA, inhibits progression of diabetic nephropathy in experimental diabetic rats. Diabetes was induced with streptozotocin in rats, and FK506 (0.5 or 1.0mg/kg) was orally administered once a day for 4 weeks. Increased relative kidney weight was significantly reduced by FK506 treatment with 1.0mg/kg (p<0.05), and elevated 24 hour urinary albumin excretion rate was markedly attenuated by FK506 treatment with 0.5 and 1.0mg/kg (p<0.05, 0.01). Elevated glomerular volume was significantly attenuated by FK506 treatment with 0.5 and 1.0mg/kg (p<0.05), and increased indices for tubulointerstitial injury were only ameliorated by FK506 treatment with 1.0mg/kg (p<0.01). Western blot analysis noted that the expression of CaN protein was increased 2.4 fold in the kidney from diabetic rats, and FK506 treatment with 0.5 and 1.0mg/kg could reduce increased expression of CaN protein by 38.0% and 73.2%. The expression of 1α (IV) collagen, p65, p-p65, OPN, α-SMA and TGF-β1 protein in kidney was significantly increased in diabetic rats and reduced by FK506 treatment (p<0.05, 0.01). Our results show that FK506 could ameliorate renal injury in early experimental diabetic rats, which mechanism may be at least partly correlated with suppression on increased CaN in renal tissue in diabetic rats.