Department of Occupational Health and Environment Health, School of Public Health, Anhui Medical University, Hefei 230032, China; Anhui Province Key Laboratory of Occupational Health, Anhui No. 2 Provincial People's Hospital, Hefei 230041, China.
Anhui Province Key Laboratory of Occupational Health, Anhui No. 2 Provincial People's Hospital, Hefei 230041, China.
Int Immunopharmacol. 2024 Dec 5;142(Pt A):113088. doi: 10.1016/j.intimp.2024.113088. Epub 2024 Sep 7.
Silica-induced pulmonary fibrosis is an irreversible and progressive lung disease with limited treatments available. In this work, FDA-approved cannabidiol (CBD) was studied for its potential medical use in silicosis. In silicosis female C57BL/6 mice model, oral CBD or pirfenidone (PFD) on day 1 after intratracheal drip silica (150 mg/mL) and continued for 42 days. Lung inflammatory and fibrotic changes were studied using ELISA kits, H&E staining and Masson staining. Osteopontion (OPN) and α-smooth muscle actin (α-SMA) expression in lung tissues was determined using immunohistochemical staining. The results indicated that CBD attenuated silica-induced pulmonary inflammation and fibrosis. Human myeloid leukemia mononuclear cells (THP-1) were treated with silica (200 μg/mL) to induce cell damage, then CBD (10 μM, 20 μM) and PFD (100 μM) were incubated. In vitro experiments showed that CBD can effectively reduce the expression of NLRP3 inflammasome in THP-1 cells and subsequently block silica-stimulated transformation of fibromuscular-myofibroblast transition (FMT) by culturing human embryonic lung fibroblasts (MRC-5) in conditioned medium of THP-1 cells. Therefore, CBD exhibited the potential therapy for silicosis through inhibiting the silica-induced pulmonary inflammation and fibrosis via the NLRP3/TGF-β1/Smad2/3 signaling pathway.
二氧化硅诱导的肺纤维化是一种不可逆转的进行性肺部疾病，治疗方法有限。在这项工作中，研究了美国食品和药物管理局批准的大麻二酚 (CBD) 在矽肺中的潜在医学用途。在矽肺雌性 C57BL/6 小鼠模型中，气管内滴注二氧化硅（150mg/mL）后第 1 天口服 CBD 或吡非尼酮（PFD），并持续 42 天。使用 ELISA 试剂盒、H&E 染色和 Masson 染色研究肺炎症和纤维化变化。使用免疫组织化学染色测定肺组织中骨桥蛋白 (OPN) 和 α-平滑肌肌动蛋白 (α-SMA) 的表达。结果表明，CBD 减轻了二氧化硅诱导的肺炎症和纤维化。用二氧化硅（200μg/mL）处理人髓样白血病单核细胞（THP-1）以诱导细胞损伤，然后孵育 CBD（10μM、20μM）和 PFD（100μM）。体外实验表明，CBD 可有效降低 THP-1 细胞中 NLRP3 炎性小体的表达，进而阻断二氧化硅刺激的纤维母细胞-肌纤维母细胞转化（FMT），方法是用 THP-1 细胞的条件培养基培养人胚肺成纤维细胞（MRC-5）。因此，CBD 通过抑制 NLRP3/TGF-β1/Smad2/3 信号通路抑制二氧化硅诱导的肺炎症和纤维化，显示出治疗矽肺的潜力。
