摘 要：癌症是全世界的一个主要致死病因。在癌症治疗中，超过65%的患者需要单独接受放疗或与其他疗法结合使用。放射性肺损伤是胸部放疗过程中的主要并发症，涉及多个阶段的复杂病理过程，主要分为放射性肺炎和放射性肺纤维化。放射性肺炎是纤维化的早期阶段，以急性肺组织炎症为特征。放射性肺纤维化是损伤的晚期阶段，其特征是肌成纤维细胞的异常激活和细胞外基质（ECM）的过度积累。放射性肺损伤限制了有效杀死肿瘤细胞的辐射剂量，是提高肺癌患者治愈率和生活质量的主要障碍。尽管确切的机制尚不清楚，但越来越多的证据表明：在基因层面，电离辐射诱导的DNA损伤和上皮间质转化（EMT）的发生直接影响放射性肺纤维化；在细胞层面，多种细胞类型和细胞因子起着至关重要的作用。肺泡上皮细胞和血管内皮细胞的损伤会导致炎症细胞和纤维细胞的聚集、Th1/Th2淋巴细胞比例的失衡、巨噬细胞的极化和募集以及肌成纤维细胞的形成等。这些均在肺纤维化进程中起到了重要作用。本文就放射性肺损伤发生过程中的细胞、信号通路与基因调控作一综述，旨在探讨对放射性肺损伤发生的认识，以期阐明启动和控制放射性肺损伤反应的关键分子介质、早期诊断及治疗的靶点，显著提高肺癌患者放射治疗的疗效，减轻胸部肿瘤患者放射治疗的副作用。
关键词：放射性肺损伤；放射性肺纤维化；细胞外基质；免疫微环境；细胞因子
中图分类号：R818 文献标志码：A DOI：10.3969/j.issn.1007-7146.2025.04.001
Abstract: Cancer is a leading cause of death worldwide. In cancer treatment, over 65% of patients require radiotherapy either alone or in combination with other therapies. Radiation-induced lung injury is a major complication during chest radiotherapy, involving a complex pathological process that spans multiple stages, primarily divided into radiation pneumonitis and radiation-induced pulmonary fibrosis. Radiation pneumonitis is the early stage of fibrosis, characterized by acute pulmonary tissue inflammation. Radiation-induced pulmonary fibrosis is the late stage of radiation-induced lung injury, characterized by the abnormal activation of myofibroblasts and excessive accumulation of extracellular matrix (ECM). Radiation-induced pulmonary fibrosis limits the radiation dose required to effectively kill tumor cells and is a major obstacle to improving the cure rate and quality of life for lung cancer patients. Although the exact mechanisms are not yet clear, a growing body of evidence suggests that, at the genetic level, ionizing radiation-induced DNA damage and epithelial-mesenchymal transition (EMT) directly affect radiation-induced pulmonary fibrosis; at the cellular level, multiple cell types and cytokines play a crucial role. Damage and differentiation of alveolar epithelial cells and vascular endothelial cells trigger the aggregation of inflammatory and fibrotic cells, imbalance of Th1/Th2 lymphocyte ratios, polarization and recruitment of macrophages, and the formation of myofibroblasts, all of which play significant roles. This article reviews the cells, signaling pathways, and gene regulation involved in the process of radiation-induced lung injury, aiming to explore the understanding of radiation-induced pulmonary fibrosis. It is hoped that this will clarify the key molecular mediators that initiate and control the radiation-induced pulmonary fibrosis response, early diagnosis, and therapeutic targets, significantly improving the efficacy of radiotherapy for lung cancer patients and reducing the side effects of radiotherapy for patients with thoracic tumors.
Key words: radiation-induced lung injury; radiation-induced pulmonary fibrosis; extracellular matrix; immune microenvironment; cytokines
（Acta Laser Biology Sinica, 2025, 34(4): 289-295）
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