Department of pathology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China; Department of Pathology, Basic Medical School, Central South University, Changsha, Hunan 410013, China; Department of pathology, Xiangya Hospital, Central South University, Changsha 410008, China.
Department of Pathology, Basic Medical School, Central South University, Changsha, Hunan 410013, China; Department of pathology, Xiangya Hospital, Central South University, Changsha 410008, China.
Ecotoxicol Environ Saf. 2024 Oct 15;285:117067. doi: 10.1016/j.ecoenv.2024.117067. Epub 2024 Sep 21.
Silicosis is one of the most severe occupational diseases characterized by inflammatory cell infiltration, fibroblasts activation, and fibrosis in the lung. However, specific drug treatments are lacking. Cardamonin (CDM) has been reported to possess antitumor, anti-inflammatory/fibrotic effects. While, the effect of CDM on the progression of silicosis remains unknown. In this study, we established a SiO-M stimulated fibroblast cell model, and explored the antifibrotic effect of CDM and the related molecular mechanism using WB, RT-qPCR, and immunofluorescence. The results indicate that CDM inhibits SiO-M-induced fibroblast activation, proliferation, and migration. Furthermore, a silicosis mouse model was established through injecting silica suspension intratracheally. The results revealed that CDM retards the progression of pulmonary fibrosis. The RNA sequencing results suggest that the antifibrotic effect of CDM may be mediated by the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. In conclusion, the results of this study demonstrate that CDM inhibits the development of silicosis via the PI3K-AKT signaling pathway, which could provide guidance for the development of drugs for silicosis treatment.
硅肺是一种最严重的职业病之一，其特征是肺部炎症细胞浸润、成纤维细胞激活和纤维化。然而，目前缺乏特定的药物治疗方法。小豆蔻明（CDM）已被报道具有抗肿瘤、抗炎/抗纤维化作用。然而，CDM 对硅肺进展的影响尚不清楚。在这项研究中，我们建立了一个 SiO-M 刺激的成纤维细胞模型，并用 WB、RT-qPCR 和免疫荧光法探讨了 CDM 的抗纤维化作用及其相关分子机制。结果表明，CDM 抑制了 SiO-M 诱导的成纤维细胞激活、增殖和迁移。此外，通过气管内注射硅酸钠混悬液建立了硅肺小鼠模型。结果表明，CDM 延缓了肺纤维化的进展。RNA 测序结果表明，CDM 的抗纤维化作用可能是通过磷脂酰肌醇 3-激酶/蛋白激酶 B（PI3K/AKT）信号通路介导的。总之，这项研究的结果表明，CDM 通过 PI3K-AKT 信号通路抑制硅肺的发展，这可为治疗硅肺的药物开发提供指导。
