Pharmacologically induced reversible hypometabolic state mitigates radiation induced lethality in mice.
Pharmacologically induced reversible hypometabolic state mitigates radiation induced lethality in mice.
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DOI：
10.1038/s41598-017-15002-7
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发表时间：
2017-11-02
影响因子：
4.6
通讯作者：
Indraganti PK
中科院分区：
文献类型：
--
作者：
Ghosh S;Indracanti N;Joshi J;Ray J;Indraganti PK
治疗性低温已被证明在许多疾病状态的重症监护中有益，其中炎症和氧化应激是关键因素。在这里，我们报道了一磷酸腺苷（AMP）在致死性全身照射（TBI）持续6小时后1-3小时触发低代谢状态（HMS），使小鼠免于辐射致死性，这种作用是通过持续低温介导的。咖啡因和腺苷A1受体（A1AR）的非选择性拮抗剂和选择性激动剂6n -环己基腺苷的研究表明，腺苷A1受体（A1AR）信号通路的参与。脑室内注射AMP也提示可能参与中枢激活AR信号。AMP以菌株和年龄无关的方式诱导HMS，不影响行为和生殖能力。AMP诱导HMS，减轻辐射诱导的氧化DNA损伤和HSPCs的丢失。在最初的3-4小时内，IL-6和IL-10水平的增加以及向抗炎环境的转变似乎是HSPCs生存增强的原因。同基因骨髓移植（BMT）研究进一步支持辐射诱导炎症在TBI后骨髓细胞丢失中的作用。我们还发现临床上合理的亚低温可以有效减轻小鼠脑外伤引起的死亡。
Therapeutic hypothermia has proven benefits in critical care of a number of diseased states, where inflammation and oxidative stress are the key players. Here, we report that adenosine monophosphate (AMP) triggered hypometabolic state (HMS), 1–3 hours after lethal total body irradiation (TBI) for a duration of 6 hours, rescue mice from radiation-induced lethality and this effect is mediated by the persistent hypothermia. Studies with caffeine and 6N-cyclohexyladenosine, a non-selective antagonist and a selective agonist of adenosine A1 receptor (A1AR) respectively, indicated the involvement of adenosine receptor (AR) signaling. Intracerebroventricular injection of AMP also suggested possible involvement of central activation of AR signaling. AMP, induced HMS in a strain and age independent fashion and did not affect the behavioural and reproductive capacities. AMP induced HMS, mitigated radiation-induced oxidative DNA damage and loss of HSPCs. The increase in IL-6 and IL-10 levels and a shift towards anti-inflammatory milieu during the first 3–4 hours seems to be responsible for the augmented survival of HSPCs. The syngeneic bone marrow transplantation (BMT) studies further supported the role of radiation-induced inflammation in loss of bone marrow cellularity after TBI. We also showed that the clinically plausible mild hypothermia effectively mitigates TBI induced lethality in mice.
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影响因子：
5.5
作者：
Bouma, Hjalmar R.;Dugbartey, George J.;Kroese, Frans G. M.
通讯作者：
Kroese, Frans G. M.
DOI：
10.3109/02841867909128188
发表时间：
1979-01-01
期刊：
ACTA RADIOLOGICA ONCOLOGY
影响因子：
--
作者：
CRIBORN, CO;RONNBACK, C
通讯作者：
RONNBACK, C
影响因子：
56.9
作者：
Blackstone, E;Morrison, M;Roth, MB
通讯作者：
Roth, MB
影响因子：
4.8
作者：
Daniels, Isadora Susan;Zhang, Jianfa;Lee, Cheng Chi
通讯作者：
Lee, Cheng Chi
影响因子：
3.4
作者：
Fliedner, TM;Graessle, D;Reimers, K
通讯作者：
Reimers, K