Exercise Physiology Research Group, Department of Movement Sciences, KU Leuven, Tervuursevest 101, 3001, Leuven, Belgium.
Laboratory of Exercise and Health, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
Eur J Appl Physiol. 2018 Apr;118(4):847-862. doi: 10.1007/s00421-018-3820-4. Epub 2018 Feb 8.
The myocellular response to hypoxia is primarily regulated by hypoxia-inducible factors (HIFs). HIFs thus conceivably are implicated in muscular adaptation to altitude training. Therefore, we investigated the effect of hypoxic versus normoxic training during a period of prolonged hypoxia ('living high') on muscle HIF activation during acute ischaemia.
Ten young male volunteers lived in normobaric hypoxia for 5 weeks (5 days per week, ~ 15.5 h per day, FO: 16.4-14.0%). One leg was trained in hypoxia (TR, 12.3% FO) whilst the other leg was trained in normoxia (TR, 20.9% FO). Training sessions (3 per week) consisted of intermittent unilateral knee extensions at 20-25% of the 1-repetition maximum. Before and after the intervention, a 10-min arterial occlusion and reperfusion of the leg was performed. Muscle oxygenation status was continuously measured by near-infrared spectroscopy. Biopsies were taken from m. vastus lateralis before and at the end of the occlusion.
Irrespective of training, occlusion elevated the fraction of HIF-1α expressing myonuclei from ~ 54 to ~ 64% (P < 0.05). However, neither muscle HIF-1α or HIF-2α protein abundance, nor the expression of HIF-1α or downstream targets selected increased in any experimental condition. Training in both TR and TR raised muscular oxygen extraction rate upon occlusion by ~ 30%, whilst muscle hyperperfusion immediately following the occlusion increased by ~ 25% in either group (P < 0.05).
Ten minutes of arterial occlusion increased HIF-1α-expressing myonuclei. However, neither normoxic nor hypoxic training during 'living high' altered muscle HIF translocation, stabilisation, or transcription in response to acute hypoxia induced by arterial occlusion.
缺氧状态下的肌细胞反应主要由缺氧诱导因子（HIFs）调节。因此，HIFs可能与高原训练中的肌肉适应有关。因此，我们研究了在长时间缺氧（“高住低训”）期间进行缺氧训练与常氧训练对急性缺血时肌肉 HIF 激活的影响。
10 名年轻男性志愿者在常压低氧环境中生活 5 周（每周 5 天，每天约 15.5 小时，FO：16.4-14.0%）。一条腿在低氧（TR，12.3% FO）中进行训练，而另一条腿在常氧（TR，20.9% FO）中进行训练。训练课程（每周 3 次）包括间歇性单侧膝关节伸展，强度为 1 次重复最大量的 20-25%。在干预前后，对腿部进行 10 分钟的动脉闭塞和再灌注。通过近红外光谱连续测量肌肉氧合状态。在闭塞前和结束时从股外侧肌中取出活检。
无论是否进行训练，闭塞都会将表达 HIF-1α 的肌核比例从约 54%升高到约 64%（P<0.05）。然而，在任何实验条件下，肌肉 HIF-1α 或 HIF-2α 蛋白丰度，或 HIF-1α 或下游靶基因的表达均未增加。在 TR 和 TR 中进行训练均可使闭塞时肌肉的氧提取率提高约 30%，而两组的肌肉再灌注后即刻的过度灌注增加约 25%（P<0.05）。
10 分钟的动脉闭塞会增加表达 HIF-1α 的肌核。然而，在“高住低训”期间进行常氧或低氧训练均未改变肌肉 HIF 易位、稳定或转录，以应对急性动脉闭塞引起的缺氧。
