Department of Respiratory Medicine, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250033, P.R. China.
Department of Cardiology, Central Hospital of Tai'an of Shandong Province, Tai'an, Shandong 271000, P.R. China.
Int J Mol Med. 2021 Mar;47(3). doi: 10.3892/ijmm.2021.4849. Epub 2021 Jan 15.
The aim of the present study was to investigate the anti‑fibrotic effects of astragaloside IV (ASV) in silicosis rats, and to further explore the potential underlying molecular mechanisms. A silica‑induced rat model of pulmonary fibrosis was successfully constructed. Hematoxylin and eosin and Masson's trichrome staining were performed to observe the pathological changes in lung tissues. Immunohistochemical analysis was used to assess the expression levels of Collagen I, fibronectin and α‑smooth muscle actin (α‑SMA). A hemocytometer and Giemsa staining were used to evaluate the cytological characteristics of the bronchoalveolar lavage fluid. ELISA was used to detect the levels of the inflammatory cytokines tumor necrosis factor‑α, interleukin (IL)‑1β and IL‑6. Reverse transcription‑quantitative PCR and western blotting were performed to detect the mRNA and protein expression levels of genes associated with the transforming growth factor (TGF)‑β1/Smad signaling pathway. ASV alleviated silica‑induced pulmonary fibrosis, and reduced the expression of collagen I, fibronectin and α‑SMA. In addition, the results of the present study suggested that the ASV‑mediated anti‑pulmonary fibrosis response may involve reduction of inflammation and oxidative stress. More importantly, ASV suppressed silica‑induced lung fibroblast fibrosis via the TGF‑β1/Smad signaling pathway, thereby inhibiting the progression of silicosis. In conclusion, the present study indicated that ASV may prevent silicosis‑induced fibrosis by reducing the expression of Collagen I, fibronectin and α‑SMA, and reducing the inflammatory response and oxidative stress, and these effects may be mediated by inhibiting the activation of the TGF‑β1/Smad signaling pathway.
本研究旨在探讨黄芪甲苷（ASV）在矽肺大鼠中的抗纤维化作用，并进一步探讨其潜在的分子机制。成功构建了二氧化硅诱导的大鼠肺纤维化模型。通过苏木精和伊红及 Masson 三色染色观察肺组织的病理变化。免疫组织化学分析用于评估胶原 I、纤维连接蛋白和α-平滑肌肌动蛋白（α-SMA）的表达水平。血球计数器和吉姆萨染色用于评估支气管肺泡灌洗液的细胞学特征。酶联免疫吸附试验用于检测肿瘤坏死因子-α、白细胞介素（IL）-1β和 IL-6 等炎症细胞因子的水平。逆转录-定量聚合酶链反应和蛋白质印迹法用于检测转化生长因子（TGF）-β1/Smad 信号通路相关基因的 mRNA 和蛋白表达水平。ASV 减轻了二氧化硅诱导的肺纤维化，降低了胶原 I、纤维连接蛋白和 α-SMA 的表达。此外，本研究结果表明，ASV 介导的抗肺纤维化反应可能涉及减少炎症和氧化应激。更重要的是，ASV 通过 TGF-β1/Smad 信号通路抑制二氧化硅诱导的肺成纤维细胞纤维化，从而抑制矽肺的进展。综上所述，本研究表明，ASV 可能通过降低胶原 I、纤维连接蛋白和 α-SMA 的表达，减少炎症反应和氧化应激，从而预防矽肺诱导的纤维化，这些作用可能是通过抑制 TGF-β1/Smad 信号通路的激活介导的。
