Abstract:

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 ［250mg/(kg·d)］ treatment group （T1, n=15）, and the high-dosage GSPE ［500mg/(kg·d)］ reatment group（T2, n=15）.　15 normal rats were used as the control group(C), and 15 normal rats were given 250mg/(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[KG*3] the DM [KG*3]group [KG*3]than [KG*3]those[KG*3] in [KG*3]the C groupP＜0.01）. 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 (P＜0.01), whereas expressions of  mRNA  and protein of BMP-7 decreased (P＜0.05) in the DM group compared with the C group. Treated animals showed a reduction in serum AGEs, proteinuria and systolic blood pressure(P＜0.05 or P＜0.01).　GSPE reduced expressions of  mRNA and protein ofCTGFin the kidneys (P＜0.01),　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(P＜0.05 or P＜0.01).  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 (P＜0.05 or P＜0.01).    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 up-regulating expression of BMP-7.

Key words: Grape seed proanthocyanidin extracts; Diabetic nephropathy; Advanced glycation end products; Connective tissue growth factor; Bone morphogenetic protein-7; Rats, Wistar