Protective effect of edaravone on hematopoietic system injury induced by ionizing radiation in mice

Qianru ZHANG; Junling ZHANG; Hongqi TIAN

doi:10.11889/j.1000-3436.2018.rrj.36.010201

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Protective effect of edaravone on hematopoietic system injury induced by ionizing radiation in mice

RADIOBIOLOGY AND RADIOMEDICINE | 更新时间：2021-12-10

- Protective effect of edaravone on hematopoietic system injury induced by ionizing radiation in mice
- Journal of Radiation Research and Radiation Processing Vol. 36, Issue 1, (2018)
- 作者机构：
  
  1.北京协和医学院中国医学科学院放射医学研究所天津市放射医学与分子核医学重点实验室天津 300192
- 作者简介：
- 基金信息：
  
  Fundamental Research Fund for CAMS&PUMC(2016ZX310199);CAMS Innovation Fund for Medical Sciences(2017-12M-3-019);National Natural Science Foundation of China(81402633);the IRM-CAMS Research and Innovation Team(创新1649)
- DOI：10.11889/j.1000-3436.2018.rrj.36.010201
  CLC：
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Qianru ZHANG, Junling ZHANG, Hongqi TIAN. Protective effect of edaravone on hematopoietic system injury induced by ionizing radiation in mice. [J]. Journal of Radiation Research and Radiation Processing 36(1):010201-7(2018)
DOI：

Qianru ZHANG, Junling ZHANG, Hongqi TIAN. Protective effect of edaravone on hematopoietic system injury induced by ionizing radiation in mice. [J]. Journal of Radiation Research and Radiation Processing 36(1):010201-7(2018) DOI： 10.11889/j.1000-3436.2018.rrj.36.010201.

摘要

随机区组法将20只C57BL/6小鼠分为对照组、依达拉奉组、4 Gy照射组、4 Gy照射+依达拉奉组，每组5只小鼠。依达拉奉用生理盐水稀释配制成浓度为45mg/mL的溶液。依达拉奉组和4G y照射+依达拉奉组小鼠于照射前30 min腹腔注射依达拉奉；对照组和4 Gy照射组小鼠于照射前30 min腹腔注射生理盐水；4 Gy照射组和4 Gy照射+依达拉奉组小鼠接受,137,Cs γ射线全身照射至吸收剂量4 Gy，剂量率0.99 Gy/min。辐照后15 d处死小鼠，血细胞分析仪检测外周血细胞计数；流式细胞术检测造血干细胞（Hematopoietic stem cell，HSC）和造血祖细胞（Hematopoietic progenitor cell，HPC）比例，及骨髓中造血干/祖细胞的活性氧（Reactive oxygen species，ROS）水平；粒系-巨核系克隆形成数目（Colony forming unit-granulocyte macrophage，CFU-GM）检测骨髓造血干/祖细胞增殖能力。结果表明：与对照组比较，4 Gy照射组小鼠外周血白细胞（White blood cell，WBC）、红细胞（Red blood cell，RBC）、血小板（Blood platelet，PLT）数目分别降低74.16%、16.63%、15.04%；骨髓中HPC、LSK（Lin,-, Sca-1,+, c-kit,+,）、CD34,+,LSK细胞比例分别降低50.99%、38.51%、14.84%；骨髓细胞CFU-GM形成数目减少93.44%；CD34,-,LSK细胞比例增加1.74倍；HPC和LSK细胞的ROS水平分别升高44.11%和61.43%；与4 Gy照射组相比，4 Gy照射+依达拉奉组小鼠外周血WBC数、RBC数分别增加58.82%、9.3%；骨髓中HPC、LSK、CD34,+,LSK细胞比例分别增加1.53倍、1.5倍和14.81%；骨髓细胞CFU-GM形成数目增加57.58%；CD34,-,LSK细胞比例降低49.17%；HPC和LSK细胞的ROS水平分别降低38.94%和55.91%（,p,<, 0.05）。结果提示，依达拉奉对电离辐射诱导的造血系统损伤具有一定的保护作用。

Abstract

Twenty C57BL/6 mice were randomly divided into four groups equally: control, edaravone, radiation (4 Gy), and radiation with edaravone (4 Gy+Eda). Edaravone was dissolved in normal saline at concentration of 45 mg/mL. Mice in the edaravone, and 4 Gy+Eda groups were injected with edaravone intraperitoneally, while mice in control, and 4 Gy groups were injected with normal saline intraperitoneally. Mice in 4 Gy, and 4 Gy+Eda groups were then irradiated by ,137,Cs γ-rays at a dose of 4 Gy under dose rate of 0.99 Gy/min 30 min after injection. Mice in these four groups were euthanized 15 d after irradiation. Hematology analyzer was used to measure cell counts in peripheral blood. Flow cytometry was used to analyze the percentage of hematopoietic stem and progenitor cells (HSPCs) in bone marrow cells, as well as the levels of reactive oxygen species (ROS) in HSPCs. Colony formation unit-granulocyte macrophage (CFU-GM) assay was used to detect the proliferation of HSPCs. The results showed that compared with those of the control group, the number of peripheral blood leucocytes (WBC), erythrocytes (RBC), and platelet (PLT) in mice in 4 Gy group decreased by 74.16%, 16.63%, and 15.04%, respectively; the percentage of HPC, LSK(Lin,-, Sca-1,+, c-kit,+,), and CD34,+,LSK cells decreased by 50.99%, 38.51%, and 14.84%, respectively; the number of CFU-GM in bone marrow cells decreased by 93.44%, and the proportion of CD34,-,LSK cells increased by 1.74 times; the levels of ROS in HPC and LSK cells increased by 44.11% and 61.43%, respectively. Compared with those of the 4 Gy group, the number of WBC and RBC in mice in 4 Gy+Eda group increased by 58.82% and 9.3%, respectively; the proportion of HPC, LSK, and CD34,+,LSK cells increased by 1.53 times, 1.5 times, and 14.81%, respectively; the number of CFU-GM in bone marrow cells increased by 57.58%, the percentage of CD34,-,LSK cells decreased by 49.17%, and the ROS levels of HPC and LSK cells decreased by 38.94% and 55.91%, respectively (,p,<, 0.05). Edaravone exhibits a protective effect on radiation-induced hematopoietic system injury.

关键词

依达拉奉辐射防护剂小鼠造血系统活性氧

Keywords

EdaravoneRadioprotectorMiceHematopoietic systemReactive oxygen species (ROS)

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