Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
Br J Pharmacol. 2011 Apr;162(8):1805-18. doi: 10.1111/j.1476-5381.2011.01206.x.
The combination of Chinese herbs, Astragali Radix and Angelicae Sinensis Radix, could alleviate renal interstitial fibrosis. Astragaloside IV (AS-IV) and ferulic acid (FA) are the two major active constituents in this combination. In this study, we employed rats with unilateral ureteral obstruction to determine whether AS-IV and FA have the same renoprotective effects and investigated the mechanisms of this action.
Renal pathological changes were evaluated after treatment with AS-IV, FA or AS-IV + FA (AF) for 10 days. Meanwhile, the expression of transforming growth factor β(1) (TGF-β(1) ), fibronectin, α-smooth muscle actin (α-SMA), phosphorylation of c-Jun NH(2) -terminal kinase (p-JNK) and nitric oxide (NO) production in kidney were determined. The expressions of fibronectin, α-SMA, mitogen-activated protein kinases [JNK, extracellular signal-regulated kinases (ERK), P38] in TGF-β(1) -treated NRK-49F cells or interleukin-1-treated HK-2 cells after AS-IV, FA or AF were assessed.
AF alleviated the infiltration of mononuclear cells, tubular atrophy and interstitial fibrosis; reduced the expression of fibronectin, α-SMA, TGF-β(1) and p-JNK; and dramatically increased the production of NO in obstructed kidneys. Neither AS-IV nor FA alone improved renal damage, but both increased NO production. AF inhibited α-SMA and fibronectin expression in NRK-49F or HK-2 cells. Furthermore, AF significantly inhibited IL-1β-induced JNK phosphorylation, without affecting ERK or P38 phosphorylation. Neither AS-IV nor FA alone had any effect on the cells.
AS-IV synergizes with FA to alleviate renal tubulointerstitial fibrosis; this was associated with inhibition of tubular epithelial-mesenchymal transdifferentiation (EMT) and fibroblast activation, as well as an increase in NO production in the kidney.
中药黄芪和当归的组合可以减轻肾间质纤维化。黄芪甲苷（AS-IV）和阿魏酸（FA）是该组合中的两种主要活性成分。在这项研究中，我们使用单侧输尿管梗阻大鼠来确定 AS-IV 和 FA 是否具有相同的肾脏保护作用，并研究了这种作用的机制。
用 AS-IV、FA 或 AS-IV+FA（AF）治疗 10 天后，评估肾脏的病理变化。同时，测定肾组织中转化生长因子-β1（TGF-β1）、纤维连接蛋白、α-平滑肌肌动蛋白（α-SMA）、c-Jun NH2-末端激酶（p-JNK）磷酸化和一氧化氮（NO）的产生。测定 TGF-β1 处理的 NRK-49F 细胞或白细胞介素-1 处理的 HK-2 细胞中 AS-IV、FA 或 AF 处理后纤维连接蛋白、α-SMA、丝裂原激活蛋白激酶[JNK、细胞外信号调节激酶（ERK）、P38]的表达。
AF 减轻了单核细胞浸润、肾小管萎缩和间质纤维化；降低了纤维连接蛋白、α-SMA、TGF-β1 和 p-JNK 的表达；并显著增加了梗阻肾脏中 NO 的产生。单独使用 AS-IV 或 FA 均不能改善肾脏损伤，但均能增加 NO 的产生。AF 抑制了 NRK-49F 或 HK-2 细胞中α-SMA 和纤维连接蛋白的表达。此外，AF 显著抑制了 IL-1β诱导的 JNK 磷酸化，而不影响 ERK 或 P38 磷酸化。单独使用 AS-IV 或 FA 对细胞均无影响。
AS-IV 与 FA 协同作用减轻肾间质纤维化；这与抑制肾小管上皮-间充质转化（EMT）和纤维母细胞激活以及增加肾脏中 NO 的产生有关。
