Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
Planta Med. 2010 Sep;76(13):1431-8. doi: 10.1055/s-0029-1240943. Epub 2010 Mar 1.
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 GeneChips. 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.
两种中药（黄芪和当归）的组合煎剂，称为 A&A，已被证明在几种动物模型中具有肾保护作用，可被视为慢性肾病的补充治疗药物。在这项研究中，采用基因组方法来鉴定阻塞性肾脏中的表达特征，这些特征可能与 A&A 的抗纤维化作用相关的分子作用有关。96 只雄性 Wistar 大鼠随机分为假手术组（sham）、SAA 组（sham+A&A）、UUO 组（单侧输尿管梗阻）和 UAA 组（UUO+A&A）。SAA 和 UAA 组大鼠每天通过口服灌胃给予 A&A（14g/kg）；sham 和 UUO 组给予等体积的水。每组各有 8 只大鼠分别在手术后 3、7 和 10 天处死。使用 Affymetrix RAE-230A GeneChips 测定肾脏中的基因表达变化。通过 RT-PCR 验证 UAA 和 UUO 之间已知基因的差异表达。结果显示，与 sham 组相比，UUO 组在 3、7 和 10 天分别有 40、65 和 104 个基因上调，30、36 和 40 个基因下调。与 UUO 组相比，UAA 组在第 3 天有 8 个基因上调，2 个基因下调，在第 10 天有 2 个基因上调。这些基因包括瞬时受体蛋白 3（TRP3）、骨髓基质细胞抗原 1（BST-1）、过氧化物酶体生物发生因子 6（PEX6）、黄嘌呤脱氢酶（XDH）、细胞色素 P450 亚家族 I 成员 A1（CYP1A1）、丝氨酸/半胱氨酸蛋白酶抑制剂 clade E 成员 1（PAI-1）、成纤维细胞生长因子 23（FGF23）和 5 个 ESTs。其中，PAI-1、FGF23 和 CYP1A1 的差异表达通过 RT-PCR 进一步得到证实。这些数据提供了证据表明，A&A 的抗纤维化作用是通过阻塞性肾病中的多种途径介导的，并且可能涉及新的机制，包括 ECM 的增加退化、ROS 反应的减少和钙磷代谢的调节。
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