[Protective effects of metformin on glomerular podocytes of type 2 diabetes model rats]

To observe the effects of metformin (MET) on podocalyxin (PCX) expression in renal tissue from type 2 diabetes mellitus (T2DM) model rats and investigate its protective effects against glomerular podocyte injury.

The rat model of T2DM was established by feeding with high-fat diet and intraperitoneal injection of low dose of streptozotocin (STZ). All the rats were divided into four groups: diabetic group (n=9), metformin group (300 mg·kg(-1)·d(-1), n=8), glibenclamide group (5 mg·kg(-1)·d(-1), n=8 ) and normal group (n=8). After 8 weeks, urinary PCX and creatinine, blood glucose (BG) and glycated hemoglobin (HbA1c) were detected in all the rats. Immunohistochemistry was used to observe the protein expression of PCX in renal tissue. Real-time polymerase chain reaction (PCR) was performed to detect mRNA expression of PCX. Pathological changes of renal tissue were observed by electron microscope.

Metformin and glyburide treatment decreased the levels of BG and HbA1c [(9.6±1.1) and (9.9±1.1) vs (15.6±1.6) mmol/L, (7.0±0.3)% and (8.0±1.0)% vs (12.4±0.6)%, all P<0.05], compared with diabetes group, while there was no statistically significant difference between the two intervention groups (P>0.05). The level of urinary PCX/urinary creatinine (UPCR) in diabetic rats were higher than that of normal group [(697±136) vs (94±25 ) ng/g, P<0.05), meanwhile the levels of protein and mRNA expression of PCX in kidney tissue reduced remarkably [(0.75±0.11) vs (3.18±0.14), (0.08±0.09) vs (1.00±0.02), both P<0.05]. Above-mentioned indicators could be ameliorated by metformin and glyburide treatment compared to normal group (P<0.05), and there were statistically significant difference between the two intervention groups [(404±83) vs (516±38) ng/g, (1.54±0.06) vs(1.06±0.10), (0.23±0.01) vs (0.16±0.04), all P<0.05)]. Further observation found that basement membrane thickness of kidney [(267±22) vs (106±10)nm )] and fusion rate of foot process (0.80±0.07 vs 0) increased in the rats of diabetic group, and metformin or glyburide treatment can significantly reduced the above changes (P<0.05), additionally, the changes were remarkable different between metformin and glyburide group [(151±17) vs (204±22 ) nm, (0.49±0.04) vs (0.57±0.03), both P<0.05)].

Metformin has protective effect on glomerular podocytes by regulating the expression of PCX in renal tissue, independent of its hypoglycemic effect.