Objective:To elucidate the protective effect of ursolic acid (UA) on the podocyte injury in diabetic nephropathy rats. Method:Streptozocin (STZ) and high-glucose and high-fat diet were used to replicate the diabetic nephropathy model in rats. The rats were divided into normal group

model group

positive drug group (Irbesartan

15 mg·kg-1)

high-dose UA group (UA-H

60 mg·kg-1) and low-dose UA group (UA-L

30 mg·kg-1). The changes in blood glucose

urine protein and renal index were observed; hematoxylin-eosin (HE) staining and periodic acid-schiff (PAS) staining were used to observe the renal pathological changes; enzyme-linked immunosorbent assay(ELISA) was adopted to detect the contents of tumor necrosis factor-α (TNF-α)

interleukin-6 (IL-6)

interleukin-1β (IL-1β)

the activity of superoxide dismutase (SOD) and the content of malonaldehyde (MDA); and Western blot was performed to detect the expressions of slit diaphragm CD2-associated protein (CD2AP) and podocin protein in nephridial tissues of the rats. Result:Compared with normal group

the blood glucose

24 h urine protein

serum and renal IL-1β

IL-6 and TNF-α

renal MDA and renal index of model group significantly increased

whereas the body mass

renal SOD activity

and renal podocin and CD2AP protein expressions significantly decreased (P<0.01). Compared with model group

UA significantly decreased the blood glucose

urine protein content

renal index

renal MDA content

and serum and renal IL-1β

IL-6 and TNF-α levels

and could increase the body mass

renal SOD activity

and renal podocin and CD2AP protein expressions of model group (P<0.05

P<0.01)

and reverse rat minor glomerular abnormalities induced by diabetes. Conclusion:UA can inhibit the pathological damage of hyperglycemia to the kidney

reduce the urinary protein and protect the renal function by protecting the action of renal podocytes and regulating the expressions of CD2AP and podocin protein.