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Factors limiting the duration of artificially induced torpor in mice.
Life Sciences in Space Research ( IF 2.5 ) Pub Date : 2019-11-11 , DOI: 10.1016/j.lssr.2019.10.008
Yuri Griko 1 , Ervin Palma 2 , Eugene Galicia 3 , Florian Selch 3
Affiliation  

The possibility of artificial induction of a torpid state in animals that do not naturally do so, as well as in humans, offers a great potential in biomedicine and in human spaceflight. However, the mechanisms of action that provide a coordinated and concomitant downregulation with a safe recovery from this state are poorly understood. In our previous study, we demonstrated that the metabolic rate of mice can be reduced by nearly 94% and can remain stable under hypothermic conditions for a prolonged period of up to 11 h. The present study was carried out in order to test the limitations and identify potential factors that can enable the safe and reversible arousal of non-hibernating mice from deep artificially-induced torpor to an active state. Results demonstrate that the energy budget may be a limiting factor for the prolongation and safe recovery from the hypometabolic state. While the continuation of torpor may be possible for additional hours, we found that a reduction of 40% or more in the plasma glucose level increases the risk of heart fibrillation, which results in death during arousal. Therefore, the plasma glucose level could be a component of the criteria indicating the reversibility of torpor.

Another important factor complementing the energetic necessity that may limit the duration of torpor in mice is a gradual reduction in body mass during torpor. Under the conditions of our experiment, body mass declines by nearly 15% after 16 h from the initiation of torpor and may continue to decline if the mice are allowed to remain in torpor longer. Extrapolation of this data suggests that there may be a critical mass relating to animal mortality and thus limiting the duration of torpor. Control and maintenance of the body mass and glucose level in a torpid animal may extend the longevity of torpor and mitigate the risk of cardiac failure during rewarming to the metabolically active state. The cardiac complications that occur during arousal from torpor in many cases could be mitigated and even avoided by applying appropriate temperature-arising kinetics and providing a sufficient dynamic range to maintain cardiac output.



中文翻译:

限制小鼠人工诱导的持续时间的因素。

在自然界不自然的动物以及人类中,人工诱发a性状态的可能性为生物医学和人类太空飞行提供了巨大的潜力。但是,对提供协调且随之而来的下调以及从该状态安全恢复的作用机理了解得很少。在我们之前的研究中,我们证明了小鼠的代谢率可以降低近94%,并且在低温条件下可以保持稳定长达11小时。进行本研究是为了测试局限性并确定可能的因素,这些因素可以使非冬眠小鼠从深层人工诱导的to变到活跃状态而安全且可逆地唤醒。结果表明,能量预算可能是从代谢不足状态延长和安全恢复的限制因素。尽管可能会持续几个小时继续进行煎熬,但我们发现血浆葡萄糖水平降低40%或更多会增加心脏颤动的风险,从而导致唤醒时死亡。因此,血浆葡萄糖水平可能是表明可逆性的标准的一部分。

补充可能会限制小鼠体内持续时间的精力充沛的必要性的另一个重要因素是,在持续进行过程中体重逐渐下降。在我们的实验条件下,从开始打火后16小时起,体重下降了近15%,如果允许小鼠在打火中停留更长时间,体重可能会继续下降。该数据的推断表明可能存在与动物死亡率有关的临界质量,因此限制了玉米粥的持续时间。控制和维持to性动物的体重和葡萄糖水平可以延长of性的寿命,并减轻在恢复为新陈代谢活动状态时心力衰竭的风险。

更新日期:2019-11-11
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