Effect Of Total Glucosides Of Paeony On The Podocyte Associated Protein In STZ-induced Diabetic Rats And Its Related Mechanism

BACKGROUND AND OBJECTIVE Diabetic nephropathy is a serious complication of diabetes mellitus and the major cause of end-stage renal disease,its incidence has increased year by year.Proteinuria is not only a cardinal manifestation of glomerular injury in diabetes,but also an important pathogenetic factor in the progression of renal dysfunction.Podocyte injury is an important factor in the occurance and development of diabetic nephropathy,podocyte slit diagrame associated protein play an important role in the maintentance of glomerular filtration barrier integrity of the structure and function.In vitro study found that macrophages and their secretion of inflammatory factors may reduce Nephrin gene promoter activity and protein expression,suggesting that inflammation plays an important role in podocyte injury.Total glucosides of paeony(TGP) was the traditional Chinese herbal medicine in our country,it has been used in a variety of autoimmune diseases. In the present study,we investigate the effect of total glucosides of paeony(TGP) on the expression of Nephrin and its mechanism in the kidney from diabetic rats.METHODS Fifty adult male Sprague-Dawley rats were devideded into five groups at random.Control group(n=10),model group(n=10),model group treated with TGP (50 mg kg^-1,by gavage,n= 10),model group treated with TGP(100 mg kg^-1,n= 10) and model group treated with TGP(200 mg kg^-1,n= 10).To induce the experimental model of diabetes,rats received a single intraperitoneal injection of STZ(60mg kg ^-1. d^-1).TGP was orally administered.Control group and model group were treated with the same vehicle alone.Eight weeks after STZ injection,the following determinations were done in samples:(1) plasma glucose(BG),liver function,kidney function and plasma lipid were determined according to standard methods;(2) 24 hours urinary albumin excretion rate(UAER) were measured by enzyme immunoassay(EIA); The expression of Nephrin,tumor necrosis factor-α(TNF-α) and NF-κB-p65 protein were determined by immunofluorescence or western blot.RESULTS Elevated AER was markedly attenuated by TGP treated.(p＜0.05). There was a finely dotted linear epithelial staining of Nephrin in control group glomeruli.In contrast,the staining of glomeruli from untreated diabetic rats was attenuated,more dispersed and clustered,this diabetic-induced loss of glomerular Nephrin expression was largly prevented in TGP-treated diabetic rats.Western blot analysis showed that the expression of Nephrin protein was reduced in the kidney from diabetic rats,but significantly increased with TGP(p＜0.01,p＜0.05).The expression of TNF-αand NF-κB-p65 protein in the kidney were significantly increased in diabetic rats,which were all significantly inhibited by TGP treated(p＜0.01).CONCLUSION TGP could decrease AER in diabetic rat,which mechanism may be at least partly correlated with upregulated the expression of Nephrin in the kidney.