Prophylactic Vitamin C Attenuates Radiation-induced Lung Injury by Modulating Macrophage Polarization and Alveolar Epithelial Cell Apoptosis / 中国生物化学与分子生物学报

ABSTRACT

With the ongoing epidemic of the Coronavirus disease in China and the widespread development of radiotherapy, radiation-induced lung injury has gradually become a clinical problem that has attracted much attention. The pathogenesis of radiation-induced lung injury is complex, involving an imbalance in the polarization state of alveolar macrophages and an upregulation of alveolar epithelial cell apoptosis. Previous studies have shown that vitamin C is an important antioxidant substance, and preventive use of vitamin C can effectively treat acute lung injury. However, whether prophylactic use of vitamin C can effectively prevent or treat lung injury caused by radioactive substances, and its specific molecular mechanism remains to be studied. The purpose of this study is to investigate whether the prophylactic use of vitamin C to treat the alveolar macrophage cell line RAW 264. 7 and human lung epithelial cells BEAS-2B can effectively control the abnormal polarization of macrophages and the abnormal apoptosis of lung epithelial cells. This study found that after 4 weeks and 8 weeks of radioactive X-ray irradiation, the expression of macrophage M1 polarization state markers such as iNOS was significantly up-regulated (P< 0. 05), and preventive use of vitamin C to treat macrophages and lung epithelial cells can alleviate the polarization state disorder of macrophages and the apoptosis of alveolar epithelial cells caused by external radiation exposure, which is manifested in the down-regulation of the expression of Cleaved Caspase3. In addition, the preventive application of vitamin C treatment can inhibit the MAPK signaling pathway activated by external radiation exposure. Further experimental results showed that the inhibition of the MAPK pathway is the key to inhibiting the M1 polarization of macrophages and the apoptosis of lung epithelial cells. In summary, our findings suggest that vitamin C may play a protective role in acute radiation-induced lung injury by inhibiting macrophage M1 polarization/ promoting macrophage M2 polarization and alleviating alveolar epithelial cell apoptosis. This study will help to better understand the process and mechanism of the preventive effect of vitamin C, a common vitamin, on radiation-induced lung injury.