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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.
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Objective:To evaluate the prevention effect of low dose pre-irradiation on irradiation-induced lung injury and its possible mechanism.Methods:Totally 320 6-week-old female C57BL/6j mice were divided into control (0 Gy), low-dose (0.5 Gy), high-dose (20 Gy) and low-dose pre-radiation(0.5 Gy+ 20 Gy)groups by the random number method, with 80 mice in each group. The mice in the low-dose and low-dose pre-irradiation groups were placed in the immobilization device under full consciousness and subjected to 0.5 Gy X-ray whole-body irradiation. 2 weeks later, the 0.5 Gy pre-irradiated mice were anesthetized and subjected to 20 Gy X-rays on chest, as the pre-radiation plus high dose radiation group. The mice in the control group were irradiated with mock irradiation (0 Gy). All mice were terminated at designed time points (24 h, 1 month, 3 months and 5 months) after completion of the irradiation schedule, with 20 mice/group at each time point. Then, lung tissues were taken from mice, and pathological changes were observed by hematoxylin-eosin (HE) staining and Masson′s trichrome staining. RT-qPCR and Western blot were used to detect the expressions of mRNAs and proteins of pulmonary fibrosis-related factors.Results:Pathological changes were observed in the lung tissues 1 month after a single high-dose 20 Gy irradiation, mainly including radiation pneumonitis and a small amount of collagen accumulation, which was more serious than low-dose pre-irradiation group, and these pathological changes became more severe when the time after irradiation increased. Meanwhile, the mRNA and protein levels of proSP-C and HOPX in the low-dose pre-irradiation group were higher than those in the high-dose group, except for proSP-C protein expression at 3 and 5 months post-irradiation. A more significant change was that the mRNA level of TGF-β1 in the high-dose group was 5.8-13.6 times higher than that in the other groups at 5 months after irradiation, as well as β-catenin mRNA ( t=4.22, 5.11, P<0.05). At the same time, in the early period (24 h and 1 month) post-irradiation, the level of vimentin protein in the low-dose pre-irradiation group was significantly higher than that in the high-dose group ( t=6.54, 4.28, P<0.05). Conclusions:When the mice were pre-irradiated with 0.5 Gy X-rays, an adaptive protective response was induced in lung tissues, resulting in the tolerance to subsequent high dose irradiation.
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Objective:To evaluate the application value of SPECT lung perfusion imaging in guiding radiotherapy path, optimizing the radiotherapy plan for lung cancer and protecting lung function during radiotherapy for locally advanced non-small cell lung cancer.Methods:In this study, 84 patients with stage Ⅲ non-resectable non-small cell lung cancer were randomly divided into the control group ( n=44) and observation group ( n=40). In the control group, radiotherapy plan based on conventional CT images was delivered, and two plans based on the lung function information suggested by conventional CT and SPECT lung perfusion imaging: P1 and P2 were given in the observation group. All patients in the observation group were finally treated according to the P2 plan. The incidence of radiation pneumonitis, and changes in lung function before and after radiotherapy were statistically compared between two groups. The dose-volume parameters of P1 and P2 were statistically compared. Results:After the plan was optimized, the incidence of radiation pneumonitis in the observation group was significantly reduced and the decline of lung function was significantly improved (both P≤0.001). The functional dose parameters were significantly improved in the P2 plans (both P<0.05), whereas the irradiation dose of organs at risk did not significantly change ( P>0.05). Conclusion:SPECT lung perfusion imaging optimizes the intensity-modulated radiotherapy plan, which can reduce the functional lung dose and increase the tumor radiotherapy dose without increasing the irradiation dose of other organs at risk.
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Ionizing radiation has proved to be most valuable in clinical diagnosis and radiotherapy. And also it is used very common in industries especially such as industrial radiography, atomic energy plant, inspectoring by gamma-ray, etc. However, inadvertent exposure to relatively high doses of ionizing radiation is capable of injuring and killing cells. The lungs, because of their rich vascularization, are vulnerable to radiation injury. It is now known that IL-6 is a pleiotrophic cytokine produced by various cells that regulates the immune reponses, acute phage reactions. We performed the immunohistochemical staining of IL-6 on radiation induced lung injury by duration, to clarify the role of IL-6 in tissue damage. IL-6 was strongly expressed in early phase of radiation from alveolar macrophages and damaged endothelial cells. These findings not only have important implications for increasing our understanding of mechanisms of radiation lung injury but they also have an impact on strategies for diagnosis and therapy of radiation damage.