School of Public Health, Anhui University of Science and Technology, Huainan 232001, China; Anhui Province Key Laboratory of Occupational Health, Anhui No. 2 Provincial People's Hospital, Hefei 230041, China.
School of Public Health, Anhui University of Science and Technology, Huainan 232001, China.
Ecotoxicol Environ Saf. 2024 Oct 15;285:117124. doi: 10.1016/j.ecoenv.2024.117124. Epub 2024 Sep 28.
Silicosis is an occupational disease caused by exposure to silica characterized by pulmonary inflammation and fibrosis, for which there is a lack of effective drugs. Glycyrrhetinic acid 3-O-β-D-glucuronide (GAMG) can treat silicosis due to its anti-inflammatory and anti-fibrotic properties. Here, the effect of therapeutic interventions of GAMG was evaluated in early-stage and advanced silicosis mouse models. GAMG significantly improved fibrotic pathological changes and collagen deposition in the lungs, alleviated lung inflammation in the BALF, reduced the expression of TNF-α, IL-6, NLRP3, TGF-β1, vimentin, Col-Ⅰ, N-cadherin, and inhibited epithelial-mesenchymal transition (EMT), thereby ameliorating pulmonary fibrosis. Moreover, the dose of 100 mg/kg GAMG can effectively prevent early-stage silicosis, while that of 200 mg/kg was recommended for advanced silicosis. In vitro and in vivo study verified that GAMG can suppress EMT through the NLRP3/TGF-β1/Smad2/3 signaling pathway. Therefore, GAMG could be a promising preventive (early-stage silicosis) and therapeutic (advanced silicosis) strategy, which provides a new idea for formulating prevention and treatment strategies.
矽肺是一种由暴露于二氧化硅引起的职业病，其特征为肺部炎症和纤维化，目前尚无有效的治疗药物。甘草次酸 3-O-β-D-葡糖苷酸（GAMG）因其具有抗炎和抗纤维化特性，可用于治疗矽肺。本研究评估了 GAMG 对早期和晚期矽肺小鼠模型的治疗干预效果。GAMG 可显著改善肺部纤维化病变和胶原沉积，减轻 BALF 中的肺部炎症，降低 TNF-α、IL-6、NLRP3、TGF-β1、波形蛋白、Col-Ⅰ、N-钙黏蛋白的表达，并抑制上皮-间充质转化（EMT），从而改善肺纤维化。此外，100mg/kg 的 GAMG 剂量可有效预防早期矽肺，而 200mg/kg 的 GAMG 剂量则适用于晚期矽肺。体内外研究证实，GAMG 可通过 NLRP3/TGF-β1/Smad2/3 信号通路抑制 EMT。因此，GAMG 可能是一种有前途的预防（早期矽肺）和治疗（晚期矽肺）策略，为制定防治策略提供了新的思路。
