Growth hormone mitigates against lethal irradiation and enhances hematologic and immune recovery in mice and nonhuman primates.
Growth hormone mitigates against lethal irradiation and enhances hematologic and immune recovery in mice and nonhuman primates.
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DOI：
10.1371/journal.pone.0011056
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发表时间：
2010-06-16
期刊：
影响因子：
3.7
通讯作者：
Chao NJ
中科院分区：
文献类型：
--
作者：
Chen BJ;Deoliveira D;Spasojevic I;Sempowski GD;Jiang C;Owzar K;Wang X;Gesty-Palmer D;Cline JM;Bourland JD;Dugan G;Meadows SK;Daher P;Muramoto G;Chute JP;Chao NJ
能够减轻辐射伤害的药物是有限的。在这项研究中，我们研究了重组人生长激素（rhGH）减轻小鼠和非人灵长类动物辐射损伤的能力。以7.5 Gy剂量照射BALB/c小鼠，照射后静脉注射rhGH，每日1次，剂量为20µg/剂，连续35天。28只小鼠中有17只（60.7%）受到rhGH的保护，而生理盐水对照组中只有3只（10.7%）存活。辐照后5天的rhGH疗程也产生了类似的结果。与生理盐水对照组相比，rhGH治疗照射的BALB/c小鼠明显加速了整体造血功能的恢复。具体而言，辐射暴露后，rhgh处理小鼠的总白细胞、CD4和CD8 T细胞亚群、B细胞、NK细胞，特别是血小板的恢复明显加快。此外，在照射后第14天采集的骨髓中，通过流式细胞术和集落形成单位测定，rhGH治疗增加了造血干细胞/祖细胞的频率，表明rhGH的作用是在造血干细胞/祖细胞水平上。rhGH主要通过其生态位介导造血作用。对非人灵长类动物进行2 Gy亚致死照射后，也观察到rhGH的类似数据。我们的数据表明，rhGH促进电离辐射暴露后的造血植入和免疫恢复，并减轻致命辐射的死亡率，即使在暴露后给药。
Medications that can mitigate against radiation injury are limited. In this study, we investigated the ability of recombinant human growth hormone (rhGH) to mitigate against radiation injury in mice and nonhuman primates. BALB/c mice were irradiated with 7.5 Gy and treated post-irradiation with rhGH intravenously at a once daily dose of 20 µg/dose for 35 days. rhGH protected 17 out of 28 mice (60.7%) from lethal irradiation while only 3 out of 28 mice (10.7%) survived in the saline control group. A shorter course of 5 days of rhGH post-irradiation produced similar results. Compared with the saline control group, treatment with rhGH on irradiated BALB/c mice significantly accelerated overall hematopoietic recovery. Specifically, the recovery of total white cells, CD4 and CD8 T cell subsets, B cells, NK cells and especially platelets post radiation exposure were significantly accelerated in the rhGH-treated mice. Moreover, treatment with rhGH increased the frequency of hematopoietic stem/progenitor cells as measured by flow cytometry and colony forming unit assays in bone marrow harvested at day 14 after irradiation, suggesting the effects of rhGH are at the hematopoietic stem/progenitor level. rhGH mediated the hematopoietic effects primarily through their niches. Similar data with rhGH were also observed following 2 Gy sublethal irradiation of nonhuman primates. Our data demonstrate that rhGH promotes hematopoietic engraftment and immune recovery post the exposure of ionizing radiation and mitigates against the mortality from lethal irradiation even when administered after exposure.
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影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ
影响因子：
20.3
作者：
Chute, John P.;Muramoto, Garrett G.;Chao, Nelson J.
通讯作者：
Chao, Nelson J.
影响因子：
15.9
作者：
MERCHAV, S;TATARSKY, I;HOCHBERG, Z
通讯作者：
HOCHBERG, Z
影响因子：
7.3
作者：
Lempereur, L;Brambilla, D;Cantarella, G
通讯作者：
Cantarella, G
影响因子：
5.6
作者：
MERCHAV, S;LAKE, M;SKOTTNER, A
通讯作者：
SKOTTNER, A