Ma Yi Long, Zhu Xiongwei, Rivera Patricia M, Tøien Øivind, Barnes Brian M, LaManna Joseph C, Smith Mark A, Drew Kelly L
Institute of Arctic Biology, Alaska Basic Neuroscience Program, Box 757000, 902 N. Koyukuk Dr., Irving I Rm. 311, University of Alaska Fairbanks, Fairbanks, AK 99775-7000, USA.
Am J Physiol Regul Integr Comp Physiol. 2005 Nov;289(5):R1297-306. doi: 10.1152/ajpregu.00260.2005. Epub 2005 Jun 23.
Although hypoxia tolerance in heterothermic mammals is well established, it is unclear whether the adaptive significance stems from hypoxia or other cellular challenge associated with euthermy, hibernation, or arousal. In the present study, blood gases, hemoglobin O2 saturation (S(O2), and indexes of cellular and physiological stress were measured during hibernation and euthermy and after arousal thermogenesis. Results show that arterial O2 tension (Pa(O2)) and S(O2) are severely diminished during arousal and that hypoxia-inducible factor (HIF)-1alpha accumulates in brain. Despite evidence of hypoxia, neither cellular nor oxidative stress, as indicated by inducible nitric oxide synthase (iNOS) levels and oxidative modification of biomolecules, was observed during late arousal from hibernation. Compared with rats, hibernating Arctic ground squirrels (Spermophilus parryii) are well oxygenated with no evidence of cellular stress, inflammatory response, neuronal pathology, or oxidative modification following the period of high metabolic demand necessary for arousal. In contrast, euthermic Arctic ground squirrels experience mild, chronic hypoxia with low S(O2) and accumulation of HIF-1alpha and iNOS and demonstrate the greatest degree of cellular stress in brain. These results suggest that Arctic ground squirrels experience and tolerate endogenous hypoxia during euthermy and arousal.
尽管变温哺乳动物的耐缺氧能力已得到充分证实，但尚不清楚其适应意义是源于缺氧，还是与恒温、冬眠或觉醒相关的其他细胞挑战。在本研究中，对冬眠、恒温及觉醒产热后的血气、血红蛋白氧饱和度（S(O2)）以及细胞和生理应激指标进行了测量。结果显示，觉醒期间动脉血氧张力（Pa(O2)）和S(O2)严重降低，且缺氧诱导因子（HIF）-1α在大脑中积累。尽管有缺氧证据，但在冬眠后期觉醒过程中，无论是细胞应激还是氧化应激，均未通过诱导型一氧化氮合酶（iNOS）水平和生物分子氧化修饰表现出来。与大鼠相比，冬眠后的北极地松鼠（Spermophilus parryii）氧合良好，在经历觉醒所需的高代谢需求期后，没有细胞应激、炎症反应、神经病理学或氧化修饰的迹象。相比之下，恒温的北极地松鼠经历轻度慢性缺氧，S(O2)较低且HIF-1α和iNOS积累，并在大脑中表现出最大程度的细胞应激。这些结果表明，北极地松鼠在恒温及觉醒过程中经历并耐受内源性缺氧。
