Objective      To determine the effect of rapamycin on podocyte autophagy and impairment in diabetic mice

and its ameliorative role in diabetic nephropathy.       Methods      A total of 48 healthy male Balb/c mice were randomly divided into 4 groups

that is

control group treated with citric acid (Control

n=12)

control mice treat

ed with rapamycin (Control+R group

n=12)

STZ group (n=12)

streptozotocin (STZ) mice intraperitoneal injected with rapamycin group (STZ+R group

n=12). Diabetic animal models were induced by intraperitoneal injection of STZ into the STZ mice. After the model establishment

mice were given rapamycin at 2 mg/(kg·48 h) through intraperitoneal injection. Serum glucose and body weight of each group were measured in 0

2

4

8 and 12 weeks after treatment. At the 12th week

24-hour urinary specimens were collected to determine albumin and creatinine levels for calculation of urinary albumin/creatinine ratio (UACR)

and the kidneys were taken and weighted to calculate kidney weight/body weight ratio (KW/BW). Renal pathological changes were observed by PAS staining. Size and number of podocyte autophagy and organelles injury were investigated by transmission electron microscopy (TEM). LC3 protein

a podocyte autophagy marker

were detected by Western blotting. Podocyte count was carried through nephrin immunofluorescence staining.       Results      Compared with control group

blood glucose

UACR and KW/BW in STZ group were increased significantly (

P

0.05). PAS staining showed thickened glomerular basement membrane and increased mesangial matrix. TEM indicated podocyte foot processes were broadened and fused

and the number of podocytes and autophagosomes were decreased. LC3-Ⅱ/LC3-Ⅰprotein ratio was significantly decreased (

P

0.01). Compared with STZ group

the mice from STZ+R group showed ameliorated glomerular pathological changes and increase in number of podocytes and autophagosomes after rapamycin treatment

alleviated organelles damage of podocytes

raised LC3-Ⅱ/LC3-Ⅰ protein ratio

and decreased UACR and KW/BW ratio (

P

0.05)

but no significant difference was seen in blood glucose.       Conclusion       Inra-peritoneal injection of rapamycin ameliorates glomerular pathological changes and podocytes injury in diabetic mice

which might be through promoting podocyte autophagy. Maintenance of po

docyte autophagic balance might be effective measure to postpone the progress of diabetic nephropathy.