Horii Yuuki, Kurata Manami, Yoshida Yuma, Sakai Hiroki, Shiina Takahiko, Shimizu Yasutake
Laboratory of Veterinary Physiology, Faculty of Applied Biological Sciences, Gifu University, Gifu, Japan.
Laboratory of Veterinary Pathology, Faculty of Applied Biological Sciences, Gifu University, Gifu, Japan.
J Vet Med Sci. 2025 Feb 4;87(2):160-166. doi: 10.1292/jvms.24-0369. Epub 2024 Dec 31.
Hibernating animals show a remarkable decrease in body temperature without accompanying serious organ damage. Active hypometabolism may be involved in the protective mechanisms. Therefore, in the present study, the phosphorylation status of Akt was used to examine whether metabolism is actively reduced during artificial hypothermia in hamsters. Hypothermia induced by activation of the central adenosine A1 receptor (A1AR) resulted in dephosphorylation of Akt in the heart, as in that of hibernating hamsters. Since phosphorylated Akt almost totally disappeared, it is probable that cellular metabolism is actively reduced in A1AR-mediated hypothermia. Surprisingly, phosphorylation of Akt was significantly, but not totally, reduced even when hypothermia was induced by a combination of inhalation anesthesia and cooling. It can thus be considered that active regulation for the reduction of metabolic activity occurs in A1AR-mediated hypothermia as well as in anesthesia-induced hypothermia, though to a lesser extent. In both hypothermic conditions, serious arrhythmias were rarely observed. In anesthesia-induced hypothermia, during which dephosphorylation of Akt occurred only partially, there was no obvious organ damage in histopathological examination. Taken together, our findings suggest that artificial hypothermia causes active hypometabolism and has therapeutically applicable properties.
冬眠动物的体温会显著下降，却不会伴随严重的器官损伤。活跃的低代谢可能参与了保护机制。因此，在本研究中，利用Akt的磷酸化状态来检测仓鼠在人工低温过程中代谢是否会主动降低。与冬眠仓鼠一样，通过激活中枢腺苷A1受体（A1AR）诱导的低温导致心脏中Akt去磷酸化。由于磷酸化的Akt几乎完全消失，在A1AR介导的低温过程中细胞代谢很可能会主动降低。令人惊讶的是，即使通过吸入麻醉和降温联合诱导低温，Akt的磷酸化也会显著但并非完全降低。因此可以认为，在A1AR介导的低温以及麻醉诱导的低温中都会发生对代谢活性降低的主动调节，尽管程度较轻。在这两种低温状态下，很少观察到严重的心律失常。在麻醉诱导的低温过程中，Akt仅发生部分去磷酸化，组织病理学检查未发现明显的器官损伤。综上所述，我们的研究结果表明，人工低温会导致活跃的低代谢，并具有治疗应用价值。
