Mitigative Effects of a Combination of Multiple Pharmaceutical Drugs on the Survival of Mice Exposed to Lethal Ionizing Radiation
Mitigative Effects of a Combination of Multiple Pharmaceutical Drugs on the Survival of Mice Exposed to Lethal Ionizing Radiation
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DOI：
10.2174/1389201016666150826125331
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发表时间：
2016-01-01
影响因子：
2.8
通讯作者：
Kashiwakura, Ikuo
中科院分区：
文献类型：
--
作者：
Hirouchi, Tokuhisa;Ito, Koichi;Kashiwakura, Ikuo
建立一套简单易行的放射事故患者应急救治方案，对减少辐射相关人员伤亡具有重要意义。本研究的目的是建立一个最佳的治疗方案，使用目前批准的药物，以增加受害者暴露于致命辐射的生存。4种药物的不同组合--重组人促红细胞生成素（EPO）、粒细胞集落刺激因子（G-CSF）、c-mpl受体激动剂罗米司亭（RP）和癸酸诺龙（ND）--在暴露于致死剂量7戈伊的γ射线后2小时内给予小鼠。在照射后第30天，使用各种血液学参数分析小鼠的状况，例如外周血细胞、骨髓细胞、造血祖细胞的数量和细胞表面抗原的表达。大约10%的未经处理的辐照对照小鼠存活了21天，但所有对照小鼠在第30天死亡。照射后立即联合给予G-CSF、EPO和RP 5天，导致照射小鼠完全存活至第30天。然而，用G-CSF、EPO和RP治疗ND在第30天仅导致75%的存活率。血液学分析显示，经有效药物治疗的存活小鼠中几乎所有造血细胞的数量恢复到未照射小鼠的水平。本研究结果表明，G-CSF，EPO和RP的组合可能是一个有用的对策，意外致死照射照射的受害者。
It is important to establish an easy-to-use therapeutic protocol for the emergency medical care of patients involved in radiation accidents to reduce the radiation-related casualties. The present study aimed to establish an optimum therapeutic protocol using currently approved pharmaceutical drugs to increase the survival of victims exposed to lethal radiation. Different combinations of four drugs-recombinant human erythropoietin (EPO), granulocyte-colony stimulating factor (G-CSF), c-mpl receptor agonist romiplostim (RP) and nandrolone decanoate (ND)-were administered to mice within 2 h after exposure to a lethal 7 Gy dose of gamma-irradiation. On day 30 after irradiation, the condition of the mice was analyzed using various hematological parameters, such as the number of peripheral blood cells, bone marrow cells, hematopoietic progenitor cells and the expression of cell surface antigens. Approximately 10% of the untreated irradiated control mice survived for 21 days, but all of the control mice died by day 30. The combined administration of G-CSF, EPO and RP for five days immediately after irradiation led to a complete survival of the irradiated mice until day 30. However, the treatment with G-CSF, EPO and RP with ND led to only 75% survival at day 30. The hematological analyses showed that the numbers of almost all of hematopoietic cells in the surviving mice treated with effective medications recovered to the levels of non-irradiated mice. The present findings show that the combination of G-CSF, EPO and RP may be a useful countermeasure for victims exposed to accidental lethal irradiation.