Effect of tacrolimus on macrophage accumulation, proliferation and activation in the kidney of early diabetic rats / 中华肾脏病杂志

ABSTRACT

ObjectiveTo investigate the effect of tacrolimus (FK506) on macrophage accumulation,proliferation and activation in the kidney of early diabetic rats and to explore its possible mechanism of renal protection.Methods Rats were randomly divided into control,model and tacrolimus groups.Diabetic model rats were induced with intraperitoneal injection of streptozotocin.Tacrolimus(0.5 or 1.0 mg·kg-1 ·d-1) was orally administered once a day for 4 weeks.Kidney weight index(KWI),24-h urinary albumin excretion rate(UAER) and creatinine clearance rate(Ccr) were measured.Kidney pathology was observed by light microscopy.ED-1,PCNAandiNOSpositivemacrophagesweredetectedbysingleanddoublestainingof immunohistochemistry.Results KWI increased in model group and was significantly reduced by tacrolimus treatment with 1.0 mg·kg-1 ·d-1 (P＜0.05).UAER elevated in model group and was markedly attenuated by tacrolimus treatment with 0.5 and 1.0 mg·kg-1 ·d-1 (P＜0.05).Elevated glomerular volume of model rats was significantly decreased by tacrolimus treatment with 0.5 and 1.0 mg·kg-1·d-1 (P＜0.05),and increased indices of tubulointerstitial injury were only ameliorated by 1.0 mg·kg-1·d-1 tacrolimus(P＜0.01).Marked accumulation of ED-1+ cells in diabetic kidney was found,which was not inhibited by tacrolimus treatment with 0.5 and 1.0 mg·kg-1·d-1.ED-1PCNA+ cells and ED-1+ iNOS+ cells were significantly elevated in kidneys of model group,while they were significantly inhibited by tacrohmus treatment with 0.5 and 1.0 mg·kg-1·d-1 (P＜0.01).Conclusion Tacrolimus can ameliorate early renal injury of diabetic rats and its mechanism may be partly associated with the suppression of increased macrophages activation.