Protective role of N-acetyl-seryl-aspartyl-lysyl-proline in renal tissue of mice with diabetic nephropathy and possible mechanisms

Objective To investigate the role and possible mechanisms of N-acetyl-seryl-aspartyl-lysyl-proline(AcSDKP) in renal tissue of mice with diabetic nephropathy(DN).Methods The mice were randomly divided into control, diabetic mellitus (DM), and DM treated with AcSDKP (DM+AcSDKP) groups. The DM model was established by a single intraperitoneal injection of streptozotocin. Natrium citricumbuffer solution of same volume was intraperitoneally injected in the control group. The DM rats in AcSDKP group were orally administrated with AcSDKP (1 mg/kg every two days) for 12 weeks. Blood and urine samples were collected before mice were sacrificed 12 weeks later. The glomerular morphology and podocyte ultrastructure were observed under the light and transmission election microscopies respectively. The expression of nephrin was detected by immunofluorescence. Western blotting was used to detect the expression of fibronectin and α-SMA proteins in the renal tissues.Results (1) Albuminuria was increased 12 weeks after streptozotocin injection. DM mice displayed foot process fusion and broadening, renal fibrosis and increased glomerular surface area. The expression of nephrin was decreased in DM group. Blood pressure had no significant change in three groups. (2)AcSDKP decreased albuminuria, alleviated foot process fusion, ameliorated glomerular hypertrophy and renal fibrosis in DM mice. (3)AcSDKP decreased the expression of renal fibronectin and α-SMA, and restored the expression of nephrin in DM mice.Conclusions AcSDKP alleviated the progression of DN via protecting against renal podocyte impairment.