Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, USA.
Department of Pediatrics and Neonatology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Int J Radiat Biol. 2020 Jan;96(1):129-144. doi: 10.1080/09553002.2018.1532619. Epub 2018 Oct 25.
Models of thoracic irradiation have been developed as clinicians and scientists have attempted to decipher the events that led up to the pulmonary toxicity seen in human subjects following radiation treatment. The most common model is that of whole thorax irradiation (WTI), applied in a single dose. Mice, particularly the C57BL/6J strain, has been frequently used in these investigations, and has greatly informed our current understanding of the initiation and progression of radiation-induced lung injury (RILI). In this review, we highlight the sequential progression and dynamic nature of RILI, focusing primarily on the vast array of information that has been gleaned from the murine model. Ample evidence indicates a wide array of biological responses that can be seen following irradiation, including DNA damage, oxidative stress, cellular senescence and inflammation, all triggered by the initial exposure to ionizing radiation (IR) and heterogeneously maintained throughout the temporal progression of injury, which manifests as acute pneumonitis and later fibrosis. It appears that the early responses of specific cell types may promote further injury, disrupting the microenvironment and preventing a return to homeostasis, although the exact mechanisms driving these responses remains somewhat unclear. Attempts to either prevent or treat RILI in preclinical models have shown some success by targeting these disparate radiobiological processes. As our understanding of the dynamic cellular responses to radiation improves through the use of such models, so does the likelihood of preventing or treating RILI.
为了解释在接受放射治疗后人类出现肺部毒性的原因，临床医生和科学家开发了多种胸部放射模型。最常见的模型是全胸照射（WTI），单次剂量应用。在这些研究中，小鼠，尤其是 C57BL/6J 品系，经常被使用，并为我们当前对放射诱导肺损伤（RILI）的发生和发展的理解提供了重要信息。在这篇综述中，我们强调了 RILI 的序贯进展和动态性质，主要关注从鼠模型中获得的大量信息。大量证据表明，照射后会出现广泛的生物学反应，包括 DNA 损伤、氧化应激、细胞衰老和炎症，所有这些反应都是由最初暴露于电离辐射（IR）引发的，并在损伤的时间进展过程中不均匀地维持，表现为急性肺炎和后期纤维化。似乎特定细胞类型的早期反应可能会促进进一步的损伤，破坏微环境并阻止其恢复到平衡状态，尽管驱动这些反应的确切机制尚不完全清楚。在临床前模型中，通过针对这些不同的放射生物学过程，试图预防或治疗 RILI 取得了一些成功。随着我们通过使用这些模型对放射后细胞动态反应的理解的提高，预防或治疗 RILI 的可能性也随之增加。
