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黄芪和当归联合依那普利对梗阻性尿路大鼠的影响。

Effect of Astragalus membranaceus and Angelica sinensis combined with Enalapril in rats with obstructive uropathy.

机构信息

Molecular and Cellular Pathology, School of Medicine, University of Queensland, Brisbane, Queensland, Australia.

出版信息

Phytother Res. 2010 Jun;24(6):875-84. doi: 10.1002/ptr.3038.

Abstract

ACE inhibitors (ACEi) reduce renal tubulointerstitial fibrosis but are not completely effective. Combined extract of Astragalus membranaceus and Angelica sinensis (A&A) is a traditional antifibrotic agent in China. The present investigation aimed to determine whether an ACEi (Enalapril) and A&A together have a better antifibrotic effect in unilateral ureteral obstruction (UUO) than monotherapy with either agent. Male Sprague-Dawley rats (N = 4 per group) had either sham operation or UUO alone, with A&A (combined aqueous and ethanol extract equivalent to 2.1 g dried herbs), with Enalapril (in drinking water at 200 mg/mL) or with both treatments. Kidney and liver were collected for protein extraction or fixed for histologic stains, immunohistochemistry (IHC), microscopy. Enalapril or A&A individually were antifibrotic. Transforming growth factor-beta1, fibroblast activation, collagen deposition, macrophage accumulation and tubular cell apoptosis were all decreased. The combination of the two drugs was significantly more effective than Enalapril alone in reducing tumor necrosis factor-alpha, collagen accumulation, activation of fibroblasts, and tubular cell apoptosis. In conclusion, Enalapril with A&A significantly decreased tubulointerstitial fibrosis to a greater extent than treatment with Enalapril alone. Further studies focusing on the isolation of the active constituents of A&A and the clinical application of the combination of ACEi plus A&A are warranted to determine the value of this treatment in humans.

摘要

血管紧张素转换酶抑制剂(ACEi)可减少肾间质纤维化,但效果并不完全。黄芪当归合剂(A&A)是中国传统的抗纤维化药物。本研究旨在探讨 ACEi(依那普利)与 A&A 联合应用是否比单独应用 ACEi 或 A&A 更能抑制单侧输尿管梗阻(UUO)大鼠的肾间质纤维化。雄性 Sprague-Dawley 大鼠(每组 4 只)行假手术或单侧输尿管梗阻术,同时给予 A&A(水提物和醇提物的混合物,相当于 2.1g 干药材)、依那普利(饮用水中浓度为 200mg/ml)或联合用药。收集肾脏和肝脏组织用于蛋白提取或行组织学染色、免疫组化(IHC)和显微镜检查。依那普利或 A&A 单独应用均具有抗纤维化作用,均可降低转化生长因子-β1、纤维母细胞激活、胶原沉积、巨噬细胞聚集和肾小管细胞凋亡。与单独应用依那普利相比,两药联合应用在降低肿瘤坏死因子-α、胶原沉积、纤维母细胞激活和肾小管细胞凋亡方面效果更为显著。总之,与单独应用依那普利相比,依那普利联合 A&A 可更显著地减轻肾间质纤维化。进一步的研究需要集中于分离 A&A 的活性成分,以及 ACEi 联合 A&A 的临床应用,以确定这种治疗方法在人类中的价值。

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