肺纤维化是对重复肺泡损伤的异常愈合反应，其特征为持续炎症和异常的胶原沉积，治疗难度大。黄芪苷(AST)是一种黄芪的有效成分，具有抗炎和抗肿瘤性能。尽管其作用机制尚不清楚，但黄芪苷也用于治疗纤维性疾病。本研究旨在研究黄芪苷在肺纤维化治疗中的作用机制。我们发现，黄芪苷显著改善了限制性通气障碍、肺顺应性、总肺容积和功能残留容积。在肺纤维化小鼠中，肺实质中的细胞外基质沉积和炎症反应得到逆转。这种治疗效果可以归因于自噬，激活自噬流和自噬泡的基因。自噬受损会通过加重体内外胶原沉积而增加肺纤维化的易感性。通过分子对接和网络药理学的结合，我们发现Ras/Raf/MEK/ERK信号通路可能是黄芪苷药理作用的可能靶点。 MEK和ERK的功能性脱磷酸化抑制了Ras/Raf/MEK/ERK信号通路，该信号通路在雷帕霉素开关处汇集，以启动自噬。抑制Ras和MEK可以调节自噬。这些发现表明，黄芪苷可能通过调节Ras/Raf/MEK/ERK信号通路，经由抑郁作用来治疗肺纤维化。版权所有 © 2022 The Authors. Elsevier Masson SAS出版。保留所有权利。

Pulmonary fibrosis is an abnormal wound-healing response to repeated alveolar injury, characterized by continuous inflammation and abnormal collagen deposition. Its treatment is problematic. Astragaloside (AST) is an active component of Astragalus membranaceus with anti-inflammatory and anti-tumor properties. Although the underlying mechanisms are unknown, AST is also used to treat fibrotic diseases. This study aimed to investigate the mechanisms of action of AST in pulmonary fibrosis treatment. We found that AST significantly improved restrictive ventilatory impairment, compliance, total lung capacity, and functional residual capacity. In mice with pulmonary fibrosis, extracellular matrix deposition in the pulmonary parenchyma and intemperate inflammation were reversed. This therapeutic effect can be attributed to autophagy, activating the genes for autophagy flux and autophagic vacuoles. Impaired autophagy increased susceptibility to pulmonary fibrosis by exacerbating collagen deposition in vitro and in vivo. Using a combination of molecular docking and network pharmacology, the Ras/Raf/MEK/ERK signaling pathway was identified as a possible candidate for the pharmacologic target of AST. Functional dephosphorylation of MEK and ERK inhibited the Ras/Raf/MEK/ERK signaling pathway, which converges at the rapamycin switch to initiate autophagy. Inhibitors of Ras and MEK regulated autophagy. These findings suggest that AST might treat pulmonary fibrosis by modulating the Ras/Raf/MEK/ERK signaling pathway mediated by depression.Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.