Current Status and Prospects of the Pathological Mechanisms and Therapeutic Drugs for Silicosis

矽肺是一种由长期吸入二氧化硅颗粒引起的慢性肺部疾病，目前仍是最主要的职业病之一。矽肺的发病机制较为复杂，了解矽肺的发病机制对发掘诊断矽肺的有效生物标志物及研发治疗矽肺的药物至关重要。病程开始时，可吸入肺泡的二氧化硅被肺泡巨噬细胞吞噬，并释放一系列炎性细胞因子，这些因子招募其他免疫细胞到损伤部位。同时，像活性氧的产生和肺泡内的脂多糖等加剧了炎症反应和细胞损伤。随着时间的推移，持续的炎症反应激活成纤维细胞，促进细胞外基质成分的沉积，导致矽肺特征性的纤维化进程。近期研究还揭示了自噬、凋亡和焦亡等细胞死亡机制在矽肺发展中起了重要作用。本文综述了矽肺的热门发病机制，重点讨论了炎症因子的释放，氧化应激、内质网应激、巨噬细胞极化、细胞程序性死亡及热门信号通路等机制，并探讨了新兴的矽肺治疗策略。Silicosis is a chronic lung disease caused by the prolonged inhalation of silica particles, and it remains one of the most prevalent occupational diseases. The pathogenesis of silicosis is complex, and understanding it is crucial for discovering effective biomarkers for diagnosis and developing therapeutic drugs. In the early stages of the disease, inhaled silica particles are engulfed by alveolar macrophages, which release a series of inflammatory cytokines, such as TNF-α, IL-1β, and IL-6. These cytokines recruit other immune cells to the site of injury. Meanwhile, the generation of reactive oxygen species (ROS) and the presence of lipopolysaccharides in the alveoli exacerbate the inflammatory response and cellular damage. Over time, persistent inflammation activates fibroblasts and promotes the deposition of extracellular matrix components, leading to the characteristic fibrosis in silicosis. Recent studies have also highlighted the roles of autophagy, apoptosis, and pyroptosis in the progression of silicosis. This review summarizes the current understanding of the pathogenesis of silicosis, focusing on mechanisms such as the release of inflammatory cytokines, oxidative stress, endoplasmic reticulum stress, macrophage polarization, programmed cell death, and key signaling pathways. It also explores emerging therapeutic strategies for silicosis.