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中药黄芪和当归对慢性嘌呤霉素氨基核苷肾病大鼠模型的抗纤维化作用

Antifibrotic effect of the Chinese herbs, Astragalus mongholicus and Angelica sinensis, in a rat model of chronic puromycin aminonucleoside nephrosis.

作者信息

Wang Haiyan, Li Jingzi, Yu Ling, Zhao Yani, Ding Wei

机构信息

Division of Nephrology, The 1st Hospital and Institute of Nephrology, Peking University, Beijing 100034, People's Republic of China.

出版信息

Life Sci. 2004 Feb 13;74(13):1645-58. doi: 10.1016/j.lfs.2003.08.036.

DOI:10.1016/j.lfs.2003.08.036
PMID:14738908
Abstract

UNLABELLED

Nephrotic syndrome has long been treated in China with two herbs, Astragalus mongholicus and Angelica sinensis, which may have antifibrotic effects.

METHODS

Rats with chronic puromycin-induced nephrosis were treated with Astragalus and Angelica 3 mL/d (n = 7) or enalapril 10 mg/kg/d (n = 7). Normal control rats (n = 7) received saline rather than puromycin, and an untreated control group (n = 7) received puromycin but no treatment. After 12 weeks, stained sections of the glomerulus and tubulointerstitium were evaluated for injury. Immunohistochemistry staining measured extracellular matrix components, transforming growth factor-beta1 (TGFbeta1), osteopontin, ED-1-positive cells, and alpha-actin. TGFbeta1 mRNA was assessed by in situ hybridization. Renin, ACE activity, angiotensin, and aldosterone were measured by radioimmunoassay or colorimetry. In the untreated rats, chronic renal injury progressed to marked fibrosis at 12 weeks. Astragalus and Angelica significantly reduced deterioration of renal function and histologic damage. Expressions of type III and IV collagen, fibronectin, and laminin also decreased significantly. This anti-fibrotic effect was similar to that of enalapril. The herbs had no effect on the renin-angiotensin system but did reduce the number of ED-1-positive, and alpha-actin positive cells and expression of osteopontin compared to untreated controls. The combination of Astragalus and Angelica retarded the progression of renal fibrosis and deterioration of renal function with comparable effects of enalapril. These effects were not caused by blocking the intrarenal renin-angiotensin system, but associated with suppression of the overexpression of TGFbeta1 and osteopontin, reduction of infiltrating macrophages, and less activation of renal intrinsic cells [corrected].

摘要

未标记

在中国,长期以来一直使用两种草药黄芪和当归治疗肾病综合征,这两种草药可能具有抗纤维化作用。

方法

用嘌呤霉素诱导大鼠慢性肾病,分别用黄芪和当归3毫升/天(n = 7)或依那普利10毫克/千克/天(n = 7)进行治疗。正常对照大鼠(n = 7)接受生理盐水而非嘌呤霉素,未治疗对照组(n = 7)接受嘌呤霉素但不进行治疗。12周后,对肾小球和肾小管间质的染色切片进行损伤评估。免疫组织化学染色检测细胞外基质成分、转化生长因子-β1(TGFβ1)、骨桥蛋白、ED-1阳性细胞和α-肌动蛋白。通过原位杂交评估TGFβ1 mRNA。通过放射免疫测定法或比色法测量肾素、ACE活性、血管紧张素和醛固酮。在未治疗的大鼠中,慢性肾损伤在12周时进展为明显的纤维化。黄芪和当归显著降低了肾功能恶化和组织学损伤。III型和IV型胶原蛋白、纤连蛋白和层粘连蛋白的表达也显著降低。这种抗纤维化作用与依那普利相似。这些草药对肾素-血管紧张素系统没有影响,但与未治疗的对照组相比,确实减少了ED-1阳性和α-肌动蛋白阳性细胞的数量以及骨桥蛋白的表达。黄芪和当归的组合延缓了肾纤维化的进展和肾功能的恶化,其效果与依那普利相当。这些作用不是通过阻断肾内肾素-血管紧张素系统引起 的,而是与抑制TGFβ1和骨桥蛋白的过度表达、减少浸润巨噬细胞以及减少肾固有细胞的活化有关[校正后] 。

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