獐牙菜苦苷对放射性肺损伤的防护作用  

Protective effects of swertiamarin against radiation⁃induced lung injury

作　　者：王瑾瑜 公利鑫 赵哲 张甘 李静怡 Wang Jinyu;Gong Lixin;Zhao Zhe;Zhang Gan;Li Jingyi(Nuclear Stress Medical Center,the Second Affiliated Hospital of Chengdu Medical College,China National Nuclear Corporation 416 Hospital,Chengdu 610051,China;College of Laboratory Medicine,Chengdu Medical College,Chengdu 610500,China)

机构地区：[1]成都医学院第二附属医院·核工业四一六医院核应激医学中心,成都610051 [2]成都医学院检验医学院,成都610500

出　　处：《中华放射医学与防护杂志》2024年第6期472-481,共10页Chinese Journal of Radiological Medicine and Protection

基　　金：四川省科技厅项目(2022ZYD0073,MZGC20230029);成都市科技项目(2022⁃YF05⁃01504⁃SN);成都市卫生健康委项目(2021008)。

摘　　要：目的探讨獐牙菜苦苷对电离辐射所致肺损伤的防护作用和机制。方法实验将人支气管上皮细胞(Beas⁃2B)和人胚肺成纤维细胞(HELF)分为对照组、10 Gy X射线照射组、照射+獐牙菜苦苷组,检测獐牙菜苦苷对X射线照射后的影响。检测射线暴露后细胞的乳酸脱氢酶(LDH)释放量、细胞的增殖情况、DNA损伤水平、活性氧(ROS)水平、脂质过氧化物水平、铁离子水平、铁死亡相关蛋白SLC7A11(xCT)及谷胱甘肽过氧化物酶(GPX4)含量变化。为了验证獐牙菜苦苷在体内对放射性肺损伤是否具有防护作用,建立放射性肺损伤小鼠模型,将C57BL/6J雄性小鼠分为对照组、照射组、照射+獐牙菜苦苷组,每组5只,对小鼠胸部进行15 Gy X射线照射,照射后30 d收集小鼠肺组织及血清。观察受照小鼠肺组织病理变化、肺组织氧化应激水平及肺组织中γ⁃H2AX、GPX4含量变化和炎性因子水平变化。结果与照射组相比,照射+獐牙菜苦苷组(130μmol/l)细胞的增殖率及克隆形成率明显上升(Beas⁃2B:t=5.50~5.92,P<0.05;HELF:t=3.79~5.51,P<0.05);LDH释放率、ROS含量、脂质过氧化物水平及铁离子含量显著降低(Beas⁃2B:t=3.00~16.99,P<0.05;HELF:t=4.10~10.97,P<0.05)。DNA损伤水平显著下降(Beas⁃2B:t=5.69~8.27,P<0.05;HELF:t=3.44~14.77,P<0.05)。xCT和GPX4蛋白表达发生上调(Beas⁃2B:t=2.90~3.27,P<0.05;HELF:t=3.01~7.07,P<0.05)。体内实验中,与照射组相比,獐牙菜苦苷预处理可有效提升小鼠肺组织中GSH和GPX4含量(t=2.31~2.65,P<0.05),降低MDA和γ⁃H2AX含量(t=2.71~4.19,P<0.05),同时降低小鼠血清中IL⁃6及IL⁃1β水平(t=3.16~4.56,P<0.05)。结论獐牙菜苦苷可以通过降低电离辐射诱导的DNA损伤和氧化应激水平,从而对电离辐射引起的肺损伤发挥防护作用,为研发新型放射性肺损伤防护剂提供思路。Objective To explore the protective effects and mechanism of swertiamarin against ionizing radiation⁃induced lung injury.Methods The human bronchial epithelial cells(Beas⁃2B)and human embryonic lung fibroblasts(HELF)were divided into control group,irradiation group,and irradiation+swertiamarin group,and the effect of swertiamarin on lung cells was detected after X⁃ray irradiation.Cells exposed to radiation were subjected to detections of lactate dehydrogenase(LDH)release,cell proliferation,and the levels of DNA damage,reactive oxygen species(ROS),lipid peroxides,and iron ions,as well as changes in the contents of ferroptosis⁃related protein SLC7A11(xCT)and glutathione peroxidase 4(GPX4).Moreover,to verify the protective effects of swertiamarin against radiation⁃induced lung injury in vivo,a mouse model of radiation⁃induced lung injury was developed.Specifically,C57BL/6J male mice were divided into three groups mentioned above,with five mice in each group.After chest irradiation with 15 Gy X⁃rays,the lung tissues and serum of the mice were collected at 30 days.The pathological changes in the lung tissues,the level of oxidative stress in these tissues,and changes in the levels ofγ⁃H2AX,GPX4,and inflammatory factors were observed.Results Compared to the radiation group,the radiation plus swertiamarin group(130μmol/l)exhibited significant increases in the proliferation rate and clone proliferation rate of cells(Beas⁃2B:t=5.50-5.92,P<0.05;HELF:t=3.79-5.51,P<0.05),significant decreases in the LDH release rate,ROS content,lipid peroxide level,and iron ion content of cells(Beas⁃2B:t=3.00-16.99,P<0.05;HELF:t=4.10-10.97,P<0.05),a significant decrease in the level of DNA damage to cells(Beas⁃2B:t=5.69-8.27,P<0.05;HELF:t=3.44-14.77,P<0.05),and increased expression of xCT and GPX4 proteins in cells(Beas⁃2B:t=2.90-3.27,P<0.05;HELF:t=3.01-7.07,P<0.05).The in vivo experiments suggested that compared to radiation alone,additional pre⁃treatment using swertiamarin significantly increased the GSH and GPX4

关 键 词：獐牙菜苦苷 放射性肺损伤 DNA损伤 铁死亡 

分 类 号：R818[医药卫生—放射医学]