Effect Of Pioglitazone On Renal Osteopotin Expression In Diabetic Rats

Objective:To investigate effect of pioglitazone on renal osteopotin expression in diabetic rats.Methods: Male Sprague Dawlry rats(n=48) were randomly divided into the normal control group(A,n=12) and the model group(n=36).Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg) in the model group rats. Blood glucose(BG) levels were detected, 72 hours after the STZ injection.Blood glucose levels were determined in blood samples collected from the tail vein.Diabetes was confirmed by determining presence of hyperglycemia three times(blood glucose concentration≥16.7mmol/L).After diabetes was confirmed, the model group rats were assigned randomly into three subgroups: the diabetic rats without treatment(B), 3 and 15 mg/kg /d pioglitazone treated diabetic rats(C and D).At the end of the 8th week, 24h urine samples were collected to examine 24h microalbuminuria.At the same time, blood glucose levels ,body weight were measured. Animals were sacrificed eight weeks after confirming high blood glucose level. Blood samples were collected to detecte serum creatinine(Scr) before the sacrifice.Kidneys were removed and weighed. Then relative kidney weight(RKW) was calculated.Stained kidney sections were observed under a light microscopy .The expression of OPN was detected by immun- ehistochemistry and OPN mRNA by reverse transcription-polymerase chain reaction(RT-PCR).Results:(1) Compared with the normal control group rats, serum creatinine(Scr),24h urinary microalbumina and Relative kidney weight(RKW)were much higher than those of other groups rats(P<0.05).Treatment with pioglitazone could markedly decrease serum creatinine(Scr),24h urinary microalbumina and Relative kidney weight(RKW)compared with untreated diabetic rats (P<0.05). Contrary to diabetic rats, blood glucose level was lower in 15mg/kg /d pioglitazone group;But 3 mg/kg /d pioglitazone group showed no change in blood glucose level((P>0.05).(2) Under light microscope,pathological changes of renal injuries were alleviated after the treatment of pioglitazone.(3)The levels of OPN protein and OPN mRNA in diabetic rats were much higher than those of normal control rats (P<0.05).After treatment with pioglitazone,the expressions of OPN and OPN mRNA were lower than those of untreated diabetic group rats (P<0.05). There were no differences in expressions of OPN and OPN mRNA bwteen treatment with 3mg/kg/d and 15mg/kg/d pioglitazone(P>0.05).Conclusions:1.Level of OPN in renal tissues increase in the diabetic rats, suggesting that OPN may take part in the pathogenesis of diabetic nephropathy.2.Pioglitazone may attenuate microalbuminuria in diabetic rats and reduce the injury of kidney in diabetic rats.The effect may be at least partly correlated with suppression of increased OPN in renal tissue in diabetic rats by pioglitazone.