Attenuating effect of Fufang Xueshuantong Capsule on kidney function in diabetic nephropathy model

Abstract

Fufang Xueshuantong Capsule (FXST) can reduce urinary albumin and whole blood viscosity in early diabetic nephropathy (DN) patients. This research aimed to investigate the effect of FXST on kidney function in DN rats and to identify the underlying molecular mechanisms. We performed Illumina RatRef-12 Expression BeadChip gene array analysis, and found that 3-month treatment with FXST significantly decreased 24-h urinary albumin, serum creatinine and blood urea nitrogen, and increased urinary creatinine in DN model rats. Kidney hypertrophy and glomerular mesangial matrix expansion were also ameliorated. Kidneys from the high-dose FXST group had 67 genes with significantly changed expression (34 increased, 33 decreased). DAVID analysis showed that the fold enrichment score of "collagen type 1" was the highest in all GO functional categories. DAVID function annotation cluster analysis indicated that the top annotation cluster included three GO function categories: "response to nutrient", "response to nutrient levels" and "response to extracellular stimulus". Based on KEGG pathway analysis, we found that the most two significant pathways were "metabolism of xenobiotics by cytochrome P450" and "drug metabolism". Real-time PCR showed that relative levels of Col1a1 (collagen type 1 alpha 1), Ctgf (connective tissue growth factor) and Tgfb1 (transforming growth factor beta 1) were significantly decreased in the FXST group, while Cyp2c23 (cytochrome P-450 family 2 subfamily C polypeptide 23) and Nphs1 (nephrin) were increased. The increased expressions of TGFβ and collagen (type 1, α2) in the kidneys of DN rats were attenuated by FXST. Our data suggest that FXST can moderate kidney function in DN rats. The mechanism may involve the BMP2-TGFβ-CTGF pathway, CYP2C23 and podocyte proteins.