Tacrolimus protects podocytes by up-regulating autophagy in type 2 diabetic model rats

Abstract

Objective To assess the effects of tacrolimus (FK506) on podocyte in type 2 diabetic model rats and to explore the potential mechanism. Methods The model rats were fed with high fat and high sugar food and combining with a low-dose of streptozotocin (STZ). They were then randomly divided into a diabetic mellitus group (DM group) and a FK506 group. A normal control group (NC group) was also set. The rats in FK506 group were given with 0.5 mg·kg-1·d-1 FK506 for 8 weeks. The biochemical parameters were measured. The changes of renal pathology and ultrastructure of podocyte were observed by the light and electron microscopy. The expression of nephrin and LC3-Ⅱ was determined by immunohistochemistry and Western blotting. Results (1) Compared with those in NC group, KW/BW, systolic blood pressure (SBP), fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), urinary albumin excretion rate (UAE) and creatinine clearance rate (Ccr) in DM group were significantly increased (all P 0.05). (2) Compared with those in NC group, the glomerular volume, mesangial cell proliferation and accumulation of mesangial matrix were increased, and the foot process became disorder and fusion in DM group, while these changes were significantly reduced in FK506 group. (3) Compared with that in NC group, the expression of nephrin and LC3-Ⅱ was decreased in DM group (all P<0.05), and both of parameters were higher in FK506 group than those in DM group (all P<0.05). Conclusion FK506 may enhance podocyte autophagy in type 2 diabetic model rats and attenuate podocyte injury. Key words: Diabetic nephropathies; Podocytes; Autophagy; Tacrolimus