谷胱甘肽过氧化物酶3修饰的间充质干细胞通过降低氧化损伤减轻放射性肺损伤OACSTPCD
Glutathione peroxidase 3-modified mesenchymal stem cells attenuate radiation-induced lung injury by reducing oxidative damage
目的 探讨谷胱甘肽过氧化物酶3(GPx3)修饰的间充质干细胞(MSC)对小鼠放射性肺损伤(RILI)的保护作用及机制.方法 20 Gy 60Co单剂量照射C59BL/6小鼠肺部,经尾静脉注射GPx3修饰的MSC,不同时间点收取肺组织,进行切片染色观察病理变化;通过实时定量PCR(qPCR)检测炎症相关因子表达水平,生化实验检测丙二醛(MDA)、H2O2和8-羟基鸟嘌呤(8-OHG)含量,反转录阻断联合双引物扩增PCR检测RNA损伤情况.结果 GPx3修饰的MSC能够显著改善辐射后肺组织的病理损伤、抑制炎症反应以及纤维化进程,GPx3修饰后MSC能够更好地清除活性氧(ROS),并减少脂质过氧化产物MDA和RNA氧化损伤的8-OHG修饰.结论 GPx3修饰的MSC通过减少ROS累积以降低氧化损伤进而减轻RILI,GPx3修饰的MSC可以提高RILI的治疗效果.
Objective To investigate the protective effect and mechanism of glutathione peroxidase 3-(GPx3)modified mesenchymal stem cells(MSC)against radiation-induced lung injury(RILI).Methods GPx3-modified MSCs were injected into the tail vein of mice whose lungs were irradiated with 20 Gy.Lung tissues were collected and sections were stained to observe pathological changes.The expression levels of inflammation-related factors were detected by real time quantitative PCR(qPCR),while the levels of malondialdehyde(MDA),H2O2,and 8-hydroxyguanine(8-OHG)were detected via biochemical experiments.Additionally,RNA damage was assessed by reverse transcription blocking combining with double primer PCR.Results GPx3-modified MSCs significantly improved the pathological damage in post-radiation lung tissues and inhibited the fibrosis process and inflammatory response.GPx3-modified MSCs were able to scavenge reactive oxygen species(ROS)more effectively,resulting in a reduction of lipid peroxidation products such as MDA and oxidative damage to RNA formation of 8-OHG.Conclusion By decreasing ROS accumulation,GPx3-modified MSCs can potentially reduce oxidative damage and attenuate RILI.GPx3-modified MSCs can improve the therapeutic efficacy against RILI.
翟瑞;台福敏;丁可昕;葛常辉;郑晓飞;付汉江
安徽医科大学基础医学院,合肥 230032||军事科学院军事医学研究院,放射生物学北京市重点实验室,北京 100850军事科学院军事医学研究院,放射生物学北京市重点实验室,北京 100850
特种医学
谷胱甘肽过氧化物酶3间充质干细胞氧化损伤放射性肺损伤8-羟基鸟嘌呤
glutathione peroxidase 3mesenchymal stem cellsoxidative damageradiation-induced lung injury8-hydroxy guanine
《军事医学》 2024 (007)
487-494 / 8
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