Astragalus mongholicus ameliorates renal fibrosis by modulating HGF and TGF-β in rats with unilateral ureteral obstruction

Astragalus mongholicus ameliorates renal fibrosis by modulating HGF and TGF-β in rats with unilateral ureteral obstruction
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DOI:
10.1631/jzus.b0820230
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发表时间:
2009-05-01
影响因子:
5.1
通讯作者:
Fan, Jun-ming
Fan, Jun-ming
中科院分区:
生物学2区
文献类型:
--
作者:
Zuo, Chuan;Xie, Xi-sheng;Fan, Jun-ming

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蒙古黄芪(Astragalus mongholicus,AM)是蒙古黄芪(Astragalus membranaceus Bge.)变种蒙古亚种(Bge.)Hsiao是一种广泛使用的传统中药。本研究探讨了AM对单侧输尿管梗阻(UUO)大鼠模型肾纤维化的潜在作用。将48只SD大鼠随机分为4组:假手术组(Sham)、未处理UUO组、AM处理(10 g/(kg center dot d))UUO组和氯沙坦处理(20 mg/(kg center dot d))UUO组(作为阳性对照)。术后7、14 d分别取肾组织行HE染色和Masson染色,观察肾组织学动态变化。采用实时荧光定量PCR、免疫组化和Western blot方法分析纤维连接蛋白(FN)、I型胶原(colI)、肝细胞生长因子(HGF)、转化生长因子-β 1(TGF-β 1)和α-平滑肌肌动蛋白(α-SMA)的表达。结果表明,与氯沙坦相似,AM通过降低TGF-β 1和α-SMA的表达,减轻UUO引起的肾损害,减少FN和colI的沉积(P < 0.05),而HGF则显著升高(P < 0.05)。结果表明,黄芪能延缓肾纤维化的进展。AM的肾脏保护作用可能与抑制肌成纤维细胞活化、诱导HGF生成、降低TGF-β 1表达有关。
Astragalus mongholicus (AM) derived from the dry root of Astragalus membranaceus Bge. var. mongolicus (Bge.) Hsiao is a widely used traditional Chinese medicine. The present study investigated the potential role of AM on renal fibrosis on a rat model of unilateral ureteral obstruction (UUO). We divided 48 Sprague-Dawley rats randomly into 4 groups: sham-operated group (Sham), untreated UUO group, AM-treated (10 g/(kg center dot d)) UUO group, and losartan-treated (20 mg/(kg center dot d)) UUO group as positive control. Haematoxylin & eosin (HE) and Masson staining were used to study the dynamic histological changes of the kidneys 7 and 14 d after operation. The expressions of fibronectin (FN), type I collagen (colI), hepatocyte growth factor (HGF), transforming growth factor-beta 1 (TGF-beta 1), and alpha-smooth muscle actin (alpha-SMA) were analyzed by real-time polymerase chain reaction (PCR), immunohistochemistry staining, and Western blot. Results show that, similar to losartan, AM alleviated the renal damage and decreased the deposition of FN and colI from UUO by reducing the expressions of TGF-beta 1 and alpha-SMA (P < 0.05), whereas HGF increased greatly with AM treatment (P < 0.05). Our findings reveal that AM could retard the progression of renal fibrosis. The renoprotective effect of AM might be related to inhibition of myofibroblast activation, inducing of HGF and reducing of TGF-beta 1 expression.