预防性使用维生素C可通过调节巨噬细胞极化和肺泡上皮细胞凋亡缓解放射性肺损伤  

Prophylactic Vitamin C Attenuates Radiation-induced Lung Injury by Modulating Macrophage Polarization and Alveolar Epithelial Cell Apoptosis

作　　者：莫慧敏 常晶[1] 周海[1] 张敬剑 郑洪珍 缪翔 孙洁 郏琴[1] MO Hui-Min;CHANG Jing;ZHOU Hai;ZHANG Jing-Jian;ZHENG Hong-Zhen;MIAO Xiang;SUN Jie;JIA Qin(Department of Respiratory and Critical Care Medicine,Shidong Hospital,Yangpu District,Shanghai 200090,China)

机构地区：[1]上海市杨浦区市东医院呼吸与危重症医学科,上海200090

出　　处：《中国生物化学与分子生物学报》2023年第6期848-856,共9页Chinese Journal of Biochemistry and Molecular Biology

基　　金：上海市杨浦区科学技术委员会,杨浦区卫生健康委员会科研课题青年项目(No.YPQ202104)。

摘　　要：随着新冠肺炎在我国的持续流行和放射疗法普遍开展,放射性肺损伤(RILI)也逐渐成为了一个备受关注的临床问题。放射性肺损伤的发病机制十分复杂,该过程涉及到肺泡巨噬细胞极化状态的失衡以及肺泡上皮细胞凋亡水平的上调。既往的研究表明,维生素C是重要的抗氧化物质,预防性使用维生素C可有效治疗急性肺损伤。然而,预防性使用维生素C是否可有效预防或治疗放射性物质导致的肺损伤,以及其具体分子机制尚待研究。该研究旨在探讨预防性使用维生素C处理肺泡巨噬细胞系RAW 264.7,以及人肺上皮细胞BEAS-2B是否能有效控制巨噬细胞的异常极化及其肺上皮细胞的异常凋亡,并研究该过程中的分子机制。本研究发现,放射性X线照射4周、8周后,巨噬细胞M1极化状态标志物例如iNOS会发生显著的表达上调(P<0.05),预防性使用维生素C处理巨噬细胞以及肺上皮细胞,能缓解放射性外照射导致的巨噬细胞极化状态紊乱以及肺泡上皮细胞凋亡,具体表现为切割胱天蛋白酶(cleaved caspase3)水平的表达下调。此外,预防性应用维生素C处理能抑制放射性外照射激活的MAPK信号通路。进一步的研究结果表明,对MAPK通路的抑制作用是抑制巨噬细胞M1极化以及肺上皮细胞凋亡的关键。总之,我们的研究结果提示,维生素C能通过抑制巨噬细胞M1极化/促进巨噬细胞M2极化以及缓解肺泡上皮细胞凋亡而发挥急性放射性肺损伤的保护作用。该研究将更深入地认识维生素C对放射性肺损伤预防作用的过程与机制。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 a

关 键 词：急性放射性肺损伤 维生素C 巨噬细胞极化 细胞凋亡 

分 类 号：Q28[生物学—细胞生物学]