Liu Meng, Liu Hui, Kang Hong, Wu Juan, Xing Puhua, Ding Xiaorui, Wei Yangyang, Kong Xiaomei
NHC Key Laboratory of Pneumoconiosis, Shanxi Province Key Laboratory of Respiratory, Department of Respiratory and Critical Care Medicine, Shanxi Medical University Affiliated First Hospital, Taiyuan 030000, China.
School of Public health, Shanxi Medical University, Taiyuan 030000, China.
Ecotoxicol Environ Saf. 2025 Jan 1;289:117534. doi: 10.1016/j.ecoenv.2024.117534. Epub 2024 Dec 11.
Silicosis is a systemic disease marked by diffuse pulmonary fibrosis resulting from prolonged inhalation of crystalline silica (CS) dust. This study aimed to examine the effects of anisodamine (ANI) on pulmonary inflammation and fibrosis in silicosis, as well as to elucidate the underlying molecular mechanisms. Animal experiments demonstrated that ANI significantly reduced alveolar structure damage and the formation of silicosis nodules in affected mice, as confirmed by pathological slides. ANI inhibited the expression of tumor necrosis factor (TNF-α) in bronchoalveolar lavage fluid (BALF) while promoting the secretion of interleukin-4 (IL-4) and interleukin-10 (IL-10). Further molecular investigations indicated a strong link between pulmonary inflammation and fibrosis, showing decreased levels of α7nAChR and increased expression of phosphorylated Janus kinase 2 (JAK2) and phosphorylated transcription factor 3 (STAT3) in the lung tissues of mice exposed to CS. The relevant molecular alterations in the lung tissue of the model group of mice were reversed by ANI. Methyllycaconitine(MLA, α7nAChR inhibitor) and RO8191 (JAK2/STAT3 agonist) could reverse the therapeutic effect of ANI in silicosis and related molecular mechanisms. The results suggest that ANI may alleviate silicosis by inhibiting pulmonary inflammation and fibrosis through modulation of the JAK2/STAT3 signaling pathway, which is mediated by α7nAChR. Coal workers can utilize ANI early on to treat and prevent silicosis.
矽肺是一种全身性疾病，其特征为长期吸入结晶二氧化硅（CS）粉尘导致弥漫性肺纤维化。本研究旨在探讨山莨菪碱（ANI）对矽肺肺部炎症和纤维化的影响，并阐明其潜在的分子机制。动物实验表明，病理切片证实，ANI可显著减轻受影响小鼠的肺泡结构损伤和矽肺结节的形成。ANI抑制支气管肺泡灌洗液（BALF）中肿瘤坏死因子（TNF-α）的表达，同时促进白细胞介素-4（IL-4）和白细胞介素-10（IL-10）的分泌。进一步的分子研究表明，肺部炎症与纤维化之间存在密切联系，在接触CS的小鼠肺组织中，α7nAChR水平降低，磷酸化的Janus激酶2（JAK2）和磷酸化的转录因子3（STAT3）表达增加。ANI可逆转模型组小鼠肺组织中的相关分子改变。甲基lycaconitine（MLA，α7nAChR抑制剂）和RO8191（JAK2/STAT3激动剂）可逆转ANI对矽肺的治疗作用及相关分子机制。结果表明，ANI可能通过调节由α7nAChR介导的JAK2/STAT3信号通路来抑制肺部炎症和纤维化，从而减轻矽肺。煤矿工人可尽早使用ANI治疗和预防矽肺。
