Abstract:

Objective   To investigate the protective effect of FK506 on glomerular podocyte injury in early diabetic nephropathy rats. Methods   Thirty-eight normal male SD rats were randomly divided into the normal control group(N, n=8), the diabetic nephropathy group(DN, n=10), the FK506 treatment group(F, n=10)， and the lotensin treatment group(L, n=10).The diabetes mellitus models were established by intra-peritoneal injection of streptozotocin at a dosage of 60mg/kg in groups DN, F and L. The rats in group F were intra-gastriced with FK506(1mg/kg·d) after 4 weeks. The rats in group L were intra-gastriced with lotensin(10mg/kg·d) after 4 weeks, and the rats in the other two groups(group DN and group N) were treated with distilled water at the same dosage after 4 weeks. Blood glucose(BS), body weight(BW) and 24-hour urine protein were detected every 4 weeks. Serum creatinine(SCr), blood urea nitrogen(BUN) and kidney weight/body weight(KW/BW) were detected at the end of 8 weeks of the drug treatment. Pathological changes of nephridial tissue were observed under a light microscope and an electron microscope. Expression of Nephrin was detected using Western blot. Results   ①SCr, BUN, KW/BW and 24-hour urine protein in groups DN, were significantly higher(P<0.05) compared with the group N. The above indicators except for BS in groups F and L were significantly lower compared with group DN(P<0.05)，and there was no significant difference between the two groups(P>0.05); ②There was no significant abnormal pathological changes of nephridial tissue in group N under the light microscope. There were significantly increased glomerular volume, proliferative mesangial cells, broaden mesangial area and thicken basement membrane in group DN. The above histopathological changes of groups F and L were less compared with group DN(P<0.05), and there was no significant pathological difference between groups F and L(P>0.05); ③Under the electron microscope, group DN showed a significantly widened glomerular basement membrane, disordered, wide and fused podocytic-process. The above lesions in groups F and L were less compared with group DN(P<0.05); ④Western blot results showed that expression of Nephrin decreased by 60.1% in group DN compared with group N. Nephrin expression was obviously recovered in groups F and L. Conclusion   FK506 may reduce urinary protein and offer renal protection in diabetic rats partly by alleviating structural and functional podocyte damage through restoring Nephrin expression in podocytes.

Key words: Diabetic nephropathy; FK506; Podocyte; Streptozotocin; Nephrin protein