Effects of grape seed proanthocyanidin extracts on advanced glycation end products and expression of bone morphogenetic protein-7 in diabetic nephropathy rats.

Objective To explore the effects of grape seed proanthocyanidin extracts(GSPE) on advanced glycation end products(AGEs),expression of connective tissue growth factor(CTGF),and bone morphogenetic protein-7(BMP-7) in diabetic rats.Methods 45 rats subjected to injection of streptozotocin(STZ) were randomly divided into the diabetic group(DM,n=15),the low-dosage GSPE [250 mg/(kg·d)] treatment group(T1,n=15),and the high-dosage GSPE [500 mg/(kg·d)] treatment group(T2,n=15).15 normal rats were used as the control group(C),and 15 normal rats were given 250 mg/(kg·d)GSPE as the treatment control group(CT).Fasting plasma glucose(FPG),serum AGEs,systolic blood pressure,24 h urinary protein and ratio of kidney weight to body weight were measured in each rat after 24 weeks.The renal pathological changes were examined with PAS staining and electron microscopy.mRNA and protein expressions of CTGF and BMP-7 in the kidneys were determined by RT-PCR,Western-blot and immunohistochemical staining,respectively.Results AGEs,blood pressure,24 h urinary protein,Ccr and ratio of kidney weight to body weight were significantly higher in the DM group than those in the C group(P0.01).Renal pathology was heavily damaged in the DM group.Expressions of mRNA and protein of CTGF increased in the DM group compared with the C group(P0.01),whereas expressions of mRNA and protein of BMP-7 decreased(P0.05) in the DM group compared with the C group.Treated animals showed a reduction in serum AGEs,proteinuria and systolic blood pressure(P0.05 or P0.01).GSPE reduced expressions of mRNA and protein of CTGF in the kidneys(P0.01),which contributed to reversal of extracellular matrix(ECM) accumulation in diabetic nephropathy(DN).GSPE increased expressions of mRNA and protein of BMP-7 in the kidneys(P0.05 or P0.01).Expressions of mRNA and protein of CTGF,Ccr and ratio of kidney weight to body weight were significantly different between the T1 and T2 group(P0.05 or P0.01).Conclusion These findings suggest that GSPE holds substantial promise for the treatment of DN,and GSPE can decrease proteinuria and attenuates the progression of nephropathy in diabetic rats.Reno-protective effects of GSPE are correlated with its suppression of AGEs,down-regulating expression of CTGF,and upregulating expression of BMP-7.