Anti-Fibrotic Effects of Astragaloside IV in Systemic Sclerosis
Anti-Fibrotic Effects of Astragaloside IV in Systemic Sclerosis
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DOI：
10.1159/000366405
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发表时间：
2014-01-01
影响因子：
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通讯作者：
Cha, Xushan
中科院分区：
文献类型：
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作者：
Qi, Qing;Mao, Yueping;Cha, Xushan
目的：观察黄芪甲苷对系统性硬化症的抗肝纤维化作用。研究方法：采用Western blot、实时定量RT-qPCR、免疫荧光染色和组织病理学方法检测治疗前后的系统性硬化症（SSc）和相应配对的正常成纤维细胞中胶原和纤连蛋白的表达。采用博莱霉素诱导的SSc小鼠模型评价药物的体内作用。结果如下：与正常成纤维细胞（NF）相比，SSc（SScF）中胶原和纤维连接蛋白的表达显著增加，黄芪甲苷（AST）可在蛋白和mRNA水平上以剂量或时间依赖的方式降低SScF中胶原和纤维连接蛋白的表达。黄芪甲苷的管理一贯减少胶原蛋白的形成和部分恢复的结构，以及抑制胶原蛋白和纤维连接蛋白的表达在皮肤病变的Ssc模型小鼠。从机制上讲，黄芪甲苷IV诱导的纤维化减少可能是由于Smad 3/Fli-1的失调，Smad 3/Fli-1是纤维化反应的主要介质和TGF-β信号传导的关键分子。黄芪甲苷还降低了p-SMAD 3的水平，并完全阻断其向核内的移位。结论：黄芪甲苷通过抑制TGF-β-Smads 3轴减轻系统性硬化症的纤维化。版权所有（C）2014 S. Karger AG，巴塞尔
Objective: To evaluate the anti-fibrotic effects of Astragaloside IV in systemic sclerosis. Methods: Treated or untreated systemic sclerosis (SSc) and normal fibroblast isolated from corresponding pairs were utilized to detect expression of collagen and fibronectin by western blot, quantitative real-time RT-PCR (RT-qPCR), immunofluorescence staining and histopathological examination. SSc mouse model induced by bleomycin was used to evaluate the effects of the drug in vivo. Results: Compared to normal fibroblast (NF), the expression of collagen and fibronectin in SSc (SScF) dramatically increased, and this could be reduced by Astragaloside IV (AST) in a dose-or time-dependent manner at both protein and mRNA levels. Administration of Astragaloside IV consistently decreased collagen formation and partially restored the structure, as well as suppressing collagen and fibronectin expression in the skin lesions of SSc-model mice. Mechanistically, Astragaloside IV-induced fibrosis reduction may be due to deregulation of Smad 3/Fli-1, the major mediators of the fibrotic response and key molecules for TGF-beta signaling. Astragaloside IV also decreased the level of p-SMAD3 and completely blocked its relocation into the nuclei. Conclusion: Astragaloside IV attenuates fibrosis by inhibiting the TGF-beta-Smads3 axis in systemic sclerosis. Copyright (C) 2014 S. Karger AG, Basel