环境与职业医学2025，Vol.42Issue(1)：103-108,6.DOI:10.11836/JEOM24290
依法卡托调控Th17/Treg细胞免疫平衡减轻小鼠矽肺纤维化
Ivacaftor modulates Th17/Treg immune homeostasis to alleviate silicosis fibrosis in mice
摘要
Abstract
[Background]Long-term exposure to free silica particles can lead to lung tissue fibrosis,ultimately progressing to silicosis.There is an urgent need to develop specific drugs for silicosis treatment.Ivacaftor,a drug approved for treating cystic fibrosis,has shown potential for treating silicosis. [Objective]To investigate the effect of ivacaftor on alleviating pulmonary fibrosis in a silicosis mouse model,and to explore its mechanisms involving modulation of the T helper 17(Th17)/regulatory T cell(Treg)immune response and related signaling pathways. [Methods]Forty-two male C57BL/6J mice(6-8 weeks old,weighing 18-22 g)were randomly divided into three groups:normal saline,silicosis model,and ivacaftor intervention groups.The treatment methods for each group were as follows:Mice received 50 µL of normal saline via tracheal instillation on days 1 and 7,and 50 μL of edible oil by oral gavage daily from days 14 to 56 in the normal saline group;mice received 50 μL of silica suspension(particle size:0.5-10 μm,concentration:50 mg·mL-1)via tracheal instillation on days 1 and 7,and 50 μL of edible oil by oral gavage daily from days 14 to 56 in the silicosis model group;mice received 50 μL of silica suspension on days 1 and 7,and ivacaftor by oral gavage at a dose of 25 mg·kg-1(based on mouse body weight)daily from days 14 to 56 in the ivacaftor intervention group.Pathological evaluation of lung tissue was conducted after HE staining.The protein expression levels of active β-catenin,α-smooth muscle actin(α-SMA),and interleukin-17A(IL-17A)were measured by Western blotting(WB).Flow cytometry(FCM)was used to assess the relative expression levels of IL-17A and Foxp3 in lung tissue. [Results]After HE staining,the normal saline group showed normal alveolar structure,while the silicosis model group exhibited significant inflammation and fibrosis.The ivacaftor intervention group showed significantly reduced inflammation and fibrosis compared to the silicosis model group.The WB results showed that,compared with the normal saline group,the silicosis model group had significantly higher levels of α-SMA and IL-17A proteins(P＜0.05).In contrast,the ivacaftor intervention group showed a significant reduction in active β-catenin and α-SMA expression,and a significant increment in IL-17A compared to the silicosis model group(P＜0.05).The FCM results indicated that both the silicosis model group and the ivacaftor intervention group showed significantly increased levels of IL-17Aand Foxp3 compared to the normal saline group(P＜0.05).However,the ivacaftor intervention group further increased IL-17A expression and reduced Foxp3 expression compared to the silicosis model group(P＜0.05). [Conclusion]Ivacaftor alleviates pulmonary fibrosis in a silicosis mouse model by promoting Th17 immune responses,inhibiting Treg im-mune responses,and downregulating the Wnt/β-catenin signaling pathway.关键词
矽肺/Th17细胞/Treg细胞/依法卡托/炎症/纤维化Key words
silicosis/Th17 cell/Treg cell/ivacaftor/inflammation/fibrosis分类
医药卫生引用本文复制引用
孙晓博,蔡倩,向关翰,杜学婷,王凯,刘志宏..依法卡托调控Th17/Treg细胞免疫平衡减轻小鼠矽肺纤维化[J].环境与职业医学,2025,42(1):103-108,6.基金项目
国家自然科学基金项目(82360640) （82360640）
宁夏自然科学基金项目(2024AAC03771) （2024AAC03771）
宁夏医科大学特殊人才启动项目(XT2023011) （XT2023011）
