Radiation-induced lung injury (RILI) is a potential complication of thoracic radiotherapy that can result in pneumonitis or pulmonary fibrosis and is associated with significant morbidity and mortality. The pathobiology of RILI is complex and includes the generation of free radicals and DNA damage that precipitate oxidative stress, endothelial cell (EC), and epithelial cell injury and inflammation. While the cellular events involved continue to be elucidated and characterized, targeted and effective therapies for RILI remain elusive. Sphingolipids are known to mediate EC function including many of the cell signaling events associated with the elaboration of RILI. Sphingosine-1-phosphate (S1P) and S1P analogs enhance EC barrier function in vitro and have demonstrated significant protective effects in vivo in a variety of acute lung injury models including RILI. Similarly, statin drugs that have pleiotropic effects that include upregulation of EC S1P receptor 1 (S1PR1) have been found to be strongly protective in a small animal RILI model. Thus, targeting of EC sphingosine signaling, either directly or indirectly, to augment EC function and thereby attenuate EC permeability and inflammatory responses, represents a novel and promising therapeutic strategy for the prevention or treatment of RILI.

放射性肺损伤（RILI）是胸部放射治疗的潜在并发症，可导致肺炎或肺纤维化，并与显着的发病率和死亡率相关。 RILI 的病理生物学很复杂，包括自由基的产生和 DNA 损伤，从而引发氧化应激、内皮细胞 (EC) 以及上皮细胞损伤和炎症。虽然所涉及的细胞事件不断被阐明和表征，但针对 RILI 的靶向有效疗法仍然难以捉摸。已知鞘脂可介导 EC 功能，包括许多与 RILI 相关的细胞信号转导事件。 1-磷酸鞘氨醇 (S1P) 和 S1P 类似物在体外增强 EC 屏障功能，并在包括 RILI 在内的多种急性肺损伤模型中显示出显着的体内保护作用。同样，具有多效作用（包括上调 EC S1P 受体 1 (S1PR1)）的他汀类药物被发现在小动物 RILI 模型中具有很强的保护作用。因此，直接或间接靶向EC鞘氨醇信号传导以增强EC功能，从而减弱EC通透性和炎症反应，代表了预防或治疗RILI的新颖且有前途的治疗策略。