Altered Expression of Gene Profiles Modulated by a Combination of Astragali Radix and Angelicae Sinensis Radix in Obstructed Rat Kidney

The decoction of a combination of two Chinese herbs, Astragali Radix (the roots of Astragalus membranaceus var. mongholicus) and Angelicae Sinensis Radix (the roots of Angelica sinensis), here named as A&A, has been demonstrated to have renoprotective effects in several animal models and may be considered as a complementary therapeutic medicine for chronic kidney disease. In this study, genomic approaches were employed to identify expression signatures in the obstructed kidney, which may be linked to the molecular actions associated with anti-fibrotic effects of A&A. Ninety-six male Wistar rats were divided randomly into sham, SAA (sham + A&A), UUO (unilateral ureteral obstruction), and UAA (UUO + A&A) groups. The rats in the SAA and UAA groups were administered A&A (14 g/kg) by oral gavage once daily; the ones in the sham and UUO groups were given equal volumes of water. Eight rats from each group were sacrificed at days 3, 7, and 10 after the operation, respectively. Changes in gene expression in the kidneys were determined using Affymetrix RAE-230A Gene-Chips. The differential expression of known genes between UAA and UUO was confirmed by RT-PCR. The results revealed that 40, 65, and 104 genes were upregulated and 30, 36, and 40 genes downregulated in UUO compared with the sham group at days 3, 7, and 10, respectively. Compared to the UUO group, eight genes were upregulated and two genes were downregulated at day 3 in the UAA group, and two genes were upregulated at day 10. These genes included transient receptor protein 3 (TRP3), bone marrow stromal cell antigen 1 (BST-1), peroxisomal biogenesis factor 6 (PEX6), xanthine dehydrogenase (XDH), cytochrome P450 subfamily I member A1 (CYP1A1), serine/cysteine proteinase inhibitor clade E member1 (PAI-1), fibroblast growth factor 23 (FGF23), and five ESTs. Among these genes, differential expression of PAI-1, FGF23, and CYP1A1 were further confirmed by RT-PCR. These data provide the evidence that the anti-fibrotic effects of A&A are mediated through multiple pathways in obstructive nephropathy, and novel mechanisms may be involved in the increasing degeneration of ECM, decreasing ROS reaction, and regulation of the calcium-phosphate metabolism.