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血小板生成素模拟物罗米司亭可完全挽救受致死性电离辐射照射的小鼠。

The thrombopoietin mimetic romiplostim leads to the complete rescue of mice exposed to lethal ionizing radiation.

机构信息

Department of Radiation Science, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori, 036-8564, Japan.

Department of Radiobiology, Institute for Environmental Sciences, 2-121 Hacchazawa, Takahoko, Rokkasho-vil. Kamikita-gun, Aomori, 039-3213, Japan.

出版信息

Sci Rep. 2018 Jul 13;8(1):10659. doi: 10.1038/s41598-018-29013-5.

DOI:10.1038/s41598-018-29013-5
PMID:30006622
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6045643/
Abstract

For the primary treatment of emergency exposure to high-dose radiation, such as in the event of a radiation accident, the top priority is the reconstitution and restoration of haematopoiesis. In most radiation accidents, drug therapy is chosen as the most suitable treatment; the chosen drug should already be approved domestically, stably supplied and regularly stockpiled. In the present study, a single administration of romiplostim (RP), an approved thrombopoietin receptor agonist, produced a 100% survival rate in C57BL/6 J mice exposed to a lethal dose (7 Gy) of Cs γ-rays, and all irradiated mice survived for more than 30 days with both 3- and 5-day consecutive administrations. By day 30, the peripheral blood cells, bone marrow cells and haematopoietic progenitor cells of the RP-administered irradiated mice had all recovered to a level that was not significantly different from that in non-irradiated mice. In contrast to myelosuppression, which did not fully recover until day 30, the expression of several bone marrow cell surface antigens recovered sooner, and DNA repair concurrently increased in haematopoietic cells, speeding the resolution of double strand breaks and reducing the rates of apoptosis. These findings suggest that RP may be a clinic-ready countermeasure to treat victims of radiation accidents.

摘要

对于紧急暴露于高剂量辐射的主要治疗,例如在辐射事故的情况下,首要任务是重建和恢复造血功能。在大多数辐射事故中,药物治疗被选为最合适的治疗方法;所选药物应已在国内获得批准,供应稳定且定期储备。在本研究中,单次给予已批准的血小板生成素受体激动剂罗米司亭(RP),可使 C57BL/6J 小鼠在接受致命剂量(7Gy)Cs γ射线照射后 100%存活,所有接受照射的小鼠在连续 3 天和 5 天给药后均存活超过 30 天。到第 30 天,接受 RP 治疗的辐照小鼠的外周血细胞、骨髓细胞和造血祖细胞均已恢复到与未辐照小鼠无显著差异的水平。与直到第 30 天才完全恢复的骨髓抑制不同,几种骨髓细胞表面抗原的表达更早恢复,同时造血细胞中的 DNA 修复也增加,从而加速双链断裂的解决并降低细胞凋亡率。这些发现表明,RP 可能是一种现成的临床对策,可用于治疗辐射事故受害者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13bd/6045643/928054b43a2c/41598_2018_29013_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13bd/6045643/82c37523a9de/41598_2018_29013_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13bd/6045643/585099be813f/41598_2018_29013_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13bd/6045643/e54fcf60b2ad/41598_2018_29013_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13bd/6045643/9c05a2d0c847/41598_2018_29013_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13bd/6045643/dbef330e1d38/41598_2018_29013_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13bd/6045643/928054b43a2c/41598_2018_29013_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13bd/6045643/82c37523a9de/41598_2018_29013_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13bd/6045643/585099be813f/41598_2018_29013_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13bd/6045643/5512e7066c0f/41598_2018_29013_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13bd/6045643/e54fcf60b2ad/41598_2018_29013_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13bd/6045643/9c05a2d0c847/41598_2018_29013_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13bd/6045643/dbef330e1d38/41598_2018_29013_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13bd/6045643/928054b43a2c/41598_2018_29013_Fig7_HTML.jpg

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