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中华损伤与修复杂志(电子版) ›› 2023, Vol. 18 ›› Issue (04) : 299 -305. doi: 10.3877/cma.j.issn.1673-9450.2023.04.005

论著

低氧环境对小鼠急性放射损伤的影响
李勇, 全勇, 傅仕艳, 冉新泽, 唐红, 柳随义, 李杰, 舒畅, 陈用来, 张静, 杨冰冰, 郝玉徽()   
  1. 400038 重庆,陆军军医大学(第三军医大学)军事预防医学系全军复合伤研究所 创伤、烧伤与复合伤国家重点实验室
    401320 重庆市巴南区中医院
  • 收稿日期:2023-04-28 出版日期:2023-08-01
  • 通信作者: 郝玉徽
  • 基金资助:
    军队后勤科研项目(ALJ19J002)

Influence of hypoxia on acute radiation injuries in mice

Yong Li, Yong Quan, Shiyan Fu, Xinze Ran, Hong Tang, Suiyi Liu, Jie Li, Chang Shu, Yonglai Chen, Jing Zhang, Bingbing Yang, Yuhui Hao()   

  1. Institute of Combined Injury of PLA, State Key Laboratory of Trauma, Burn and Combined Injury, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing 400038, China
    Banan Hospital of TCM, Chongqing 401320, China
  • Received:2023-04-28 Published:2023-08-01
  • Corresponding author: Yuhui Hao
引用本文:

李勇, 全勇, 傅仕艳, 冉新泽, 唐红, 柳随义, 李杰, 舒畅, 陈用来, 张静, 杨冰冰, 郝玉徽. 低氧环境对小鼠急性放射损伤的影响[J/OL]. 中华损伤与修复杂志(电子版), 2023, 18(04): 299-305.

Yong Li, Yong Quan, Shiyan Fu, Xinze Ran, Hong Tang, Suiyi Liu, Jie Li, Chang Shu, Yonglai Chen, Jing Zhang, Bingbing Yang, Yuhui Hao. Influence of hypoxia on acute radiation injuries in mice[J/OL]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2023, 18(04): 299-305.

目的

通过建立低氧急性放射损伤动物模型研究低氧对急性放射损伤的影响,为高原急性放射损伤救治提供实验依据。

方法

模拟高原4 000 m海拔低氧环境,建立C57小鼠低氧急性放射损伤模型。将150只8~10周龄C57雄性小鼠随机分配至常氧对照组、常氧放射组、缺氧对照组、预缺氧放射组、持续缺氧放射组,每组30只。进行辐照生存率实验,记录不同时间点小鼠体重和精神状态,辐照后第3、7、14、21天血浆低氧诱导因子-1α(HIF-1α)含量、血常规、骨髓有核细胞计数和骨髓病理;检测辐照后第3、7天血浆促红细胞生成素(EPO)和转化生长因子β(TGF-β)含量。

结果

辐照后第3、7、14、21天,持续缺氧放射组出现明显骨髓组织损伤,持续缺氧放射组血浆HIF-1α含量较常氧放射组升高(q=4.660、3.346、4.978、6.759,P<0.05),表明低氧急性放射损伤模型建立成功。预缺氧放射组与常氧放射组、持续缺氧放射组相比,小鼠生存率明显提高;辐照后第7、14、21天外周血白细胞、淋巴细胞在恢复期升高更快,骨髓病理损伤更轻,骨髓有核细胞计数更多,同时辐照后小鼠体重增长更快。辐照后第3、7天,持续缺氧放射组血浆EPO含量及TGF-β含量较预缺氧放射组高(q=4.851、4.445,P<0.05;q=5.220、5.824,P<0.05)。

结论

预缺氧处理可能减轻急性放射损伤,而辐照后继续缺氧处理可能不利于急性放射损伤的恢复。

Objective

To study the effect of hypoxia on acute radiation injuries by establishing an experimental animal model of hypoxia combined with acute radiation injuryes, and provide experimental evidence for the treatment of acute radiation injuries on the plateau.

Methods

An experimental C57 mouse model of hypoxia combined with acute radiation injuryes was etablished in a low-oxygen environment which has the same oxygen concentration as the plateau of 4 000 m altitude. 150 C57 male mouses which aged 8-10 weeks were randomly divided into the normoxia control group, normoxia and radiation group, hypoxia control group, pre-hypoxia and radiation group and continuous-hypoxia and radiation group, with 30 mouses in each group. Completed the survival experiments after irradiation, recorded the weight and mental status of the mouse at different time points, and recorded the HIF-1α level of plasma, blood routine, bone marrow nucleated cell count and bone marrow pathology after irradiation on the 3th, 7th, 14th and 21st day. Besides, the levels of EPO and TGF-β in plasma were measured on the 3th and 7th day after irradiation.

Results

On the 3th, 7th, 14th and 21st day after irradiation, the continuous-hypoxia and radiation group occured significant bone marrow injury and it′s HIF-1α content of plasma was higher than that in the normoxia and radiation group (q=4.660, 3.346, 4.978, 6.759; P<0.05), indicated that the model of hypoxia combined with acute radiation injuryes was etablished successfully. Compared with the normoxia and radiation group and the continuous-hypoxia and radiation group, the pre-hypoxia and radiation group had higher survival rate. It′s peripheral blood white blood cells and lymphocytes recovered faster after irradiation on the 7th, 14th and 21st day. It's bone marrow had less pathological damage. It had more nucleated cells in bone marrow. And mouses in pre-hypoxia and radiation group gained weight faster. On the 3th and 7th after irradiation, EPO and TGF-β content of plasma in the continuous-hypoxia and radiation group were higher than those in the pre-hypoxia and radiation group(q=4.851, 4.445, P<0.05; q=5.220, 5.824, P<0.05).

Conclusion

Pre-hypoxia may mitigate acute radiation damage, while continuous hypoxia treatment after irradiation may be detrimental to recovery from acute radiation injury.

图1 辐照后各时间点骨髓病理(HE,400×)
图2 辐照后各时间点血浆HIF-1α含量。与常氧放射组相比,*P<0.05,**P<0.01;与常氧对照组相比,#P<0.05,##P<0.01
图3 致死剂量辐照后30 d内各组生存情况(按死亡数加权的个案)
图4 各观察时间点小鼠体重变化
图5 辐照后第3、7、14、21天外周血血常规。A示辐照后第3天外周血血常规;B示辐照后第7天外周血血常规;C示辐照后第14天外周血血常规;D示辐照后第21天外周血血常规。与常氧对照组相比,*P<0.05,**P<0.01
表1 股骨骨髓有核细胞计数(×106)
图6 辐照第3、7天血浆EPO和TGF-β含量。与持续缺氧放射组相比,*P<0.05,**P<0.01;与常氧对照组相比,#P<0.05,##P<0.01
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