Silicosis is an occupational pulmonary fibrosis that is caused by inhalation of silica (SiO2), and there are no effective drugs to treat this disease. Tanshinone IIA (Tan IIA), a natural product, has been reported to possess antioxidant and anti-fibrotic properties in various diseases. The purpose of the current study was to examine Tan IIA's protective effects against silica-induced pulmonary fibrosis and to explore the underlying mechanisms. We found that in vivo treatment with Tan IIA significantly relieved silica-induced lung fibrosis in a silicosis rat model by histological and immunohistochemical analyses. Further, in vitro mechanistic investigations, mainly using western blot and immunofluorescence analyses, revealed that Tan IIA administration markedly inhibited the silica-induced epithelial-mesenchymal transition (EMT) and transforming growth factor-β1 (TGF-β1)/Smad signaling pathway and also reduced silica-induced oxidative stress and activated the nuclear factor erythroid 2-related factor-2 (Nrf2) signaling pathway in A549 and human bronchial epithelial (HBE) cells. Furthermore, through transfection with siRNA, we demonstrate that Nrf2 activation partially mediates the suppression effects of Tan IIA on EMT and TGF-β1/Smad signaling pathway activation induced by silica exposure, thus mediating the anti-fibrotic effects of Tan IIA against silica-induced pulmonary fibrosis. In our study, Tan IIA has been identified as a possible anti-oxidative and anti-fibrotic drug for silicosis.

中文翻译：

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丹参酮IIA通过Nrf2介导的EMT和TGF-β1/ Smad信号转导的抑制作用减轻二氧化硅诱导的肺纤维化。

矽肺病是由吸入二氧化硅（SiO2）引起的职业性肺纤维化，目前尚无有效的药物可治疗这种疾病。据报道，天然产物丹参酮IIA（Tan IIA）在多种疾病中均具有抗氧化和抗纤维化特性。本研究的目的是研究Tan IIA对二氧化硅诱导的肺纤维化的保护作用并探讨其潜在机制。我们发现，通过组织学和免疫组织化学分析，以Tan IIA进行的体内治疗可显着缓解矽肺大鼠模型中的二氧化硅诱导的肺纤维化。此外，主要使用Western印迹和免疫荧光分析进行体外机制研究，揭示了Tan IIA给药显着抑制了二氧化硅诱导的上皮-间充质转化（EMT）和转化生长因子-β1（TGF-β1）/ Smad信号通路，并且还降低了二氧化硅诱导的氧化应激并激活了核因子类红细胞2相关A549和人支气管上皮（HBE）细胞中的NF-2信号通路。此外，通过转染siRNA，我们证明Nrf2激活部分介导了Tan IIA对二氧化硅暴露诱导的EMT和TGF-β1/ Smad信号通路激活的抑制作用，从而介导了Tan IIA对二氧化硅诱导的抗纤维化作用肺纤维化。在我们的研究中，Tan IIA被确定为矽肺病的一种可能的抗氧化和抗纤维化药物。