Study Of The Effects Of Pioglitazone On The Expressions Of Vascular Endothelia Growth Factor And Pocodin In The Kindey Of Diabetic Rats With Diabetic Nephropathy

Objective:To investigate the changes about excretion of urine protein,renal function and the expressions of VEGF and podocin in rats with diabetic nephropathy (DN),and the relationship among these changes,study the effects of pioglitazone on the expressions of vascular endothelial growth factor and podocin in the kidney of rats with diabetic nephropathyMethods:1,Diabetic rats model were established by injection of streptozotocin(55mg/kg). The model rats were divided randomly into 2 groups:pioglitazone-treated group (DP group),and model control group(DM group),nomal rats group(NC group) served as control.2,Eight weeks later,blood glucose,serum lipid profile,excretion of urine protein and renal function were detected.The expression of VEGF protein was detected by immunohistochemistry and the expressions of VEGF and podocin mRNA were detected by Reverse transcription-PCR.Histomorphologic changes were observed by optics microscope and electron microscope.Results:1,Eigh weeks later,compared with normal rats,blood glucose,excretion of urine protein,blood urea nitrogen(BUN)and serum creatinine(SCr)were significantly increased in DM group,while excretion of urine protein,blood urea nitrogen(BUN) and serum creatinine(SCr)were descreased after treated by pioglitazone.2,The expressions of VEGF protein and mRNA in the kidney of DM group were both significantly higher than NC group,whereas the expression of podocin mRNA in the kidney of DM group was significantly lower than NC group;the expressions of VEGF protein and mRNA in the kidney of DP group were both significantly descreased after treated by pioglitazone,and the expression of podocin mRNA in the kidney of DP group was significantly increased after treated by pioglitazone.3,Respectively compared with DM group,blood glucose,triglyceride,total cholesterol,high density lipoprotein cholesterol and low density lipoprotein cholesterol in DP group did not differ significantly. 4,Renal histopathological changes in DM gruop were similar to those of diabetic nephropathy.Glomerular hypertrophy,mesangial cell proliferation,extracellular matrix accumulation were observed by optics microscope in DM group.The result of electron microscope showed that podocytes were tumefied,foot processes were fusioned into a band and adhered to the basement membrane in DM group.Above abnormal histomorphologic changes were improved in DP group.5,The levels of VEGF protein and mRNA were positive correlated with 24h urine protein excretion(r=0.717,P<0.01;r=0.697,P<0.01) and the level of podocin mRNA was significantly negative correlated with 24h urine protein excretion(r=—0.603,P<0.01);the levels of VEGF protein and mRNA were positive correlated with serum creatinine(SCr)(r=0.448,P<0.05;r=0.611,P<0.01) and the level of podocin mRNA was significantly negative correlated with serum creatinine(SCr)(r=—0.635, P<0.01).Conclusion:Pioglitazone may decrease proteinuria,improve renal function, alleviate renal histopathological damage and retrieve the changes of podocin and VEGF expressions to alleviate renal filtration barrier function in DN rats,but it do not significantly change blood glucose and serum lipid profile in DP group.Pioglitazone may up-regulate podocin expression and down-regulate VEGF expression to produce direct nephroprotective effect independent of glucose and lipid metabolism.