Skovgaard Dorthe, Kjaer Michael, Madsen Jacob, Kjaer Andreas
Institute of Sports Medicine, Bispebjerg Hospital and Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
J Nucl Med. 2009 Jun;50(6):950-8. doi: 10.2967/jnumed.109.062216. Epub 2009 May 14.
The purpose of the present study was to investigate exercise-related changes in oxygenation in rat skeletal muscles and tendons noninvasively with PET/CT and the hypoxia-selective tracer (64)Cu-diacetyl bis(N(4)-methylthiosemicarbazone) (ATSM) and to quantitatively study concomitant changes in gene expression of 2 hypoxia-related genes, hypoxia-inducible factor 1alpha (HIF1alpha) and carbonic anhydrase III (CAIII).
Two groups of Wistar rats performed 1-leg contractions of the calf muscle by electrostimulation of the sciatic nerve. After 10 min of muscle contractions, (64)Cu-ATSM was injected and contractions were continued for 20 min. PET/CT of both hind limbs was performed immediately and 1 h after the contractions. The exercise group (n = 8) performed only muscle contractions as described, whereas the other group, exercise plus cuff (n = 8), in addition underwent cuff-induced hypoxia during the first PET/CT scan. Standardized uptake values (SUVs) were calculated for the Achilles tendons and triceps surae muscles and were correlated to gene expression of HIF1alpha and CAIII using real-time polymerase chain reaction.
Immediately after the contractions, uptake of (64)Cu-ATSM was significantly increased, by approximately 1.5-fold in muscles and 1.3-fold in tendons, compared with resting conditions. The significant increase was maintained in late PET scans in stimulated muscles and tendons independently of cuff application. In muscles, SUV correlated significantly with gene expression of HIF1alpha and CAIII, whereas this coherence was not found in tendons.
We found enhanced uptake of (64)Cu-ATSM in both early and late PET scans, thereby supporting the possibility that (64)Cu-ATSM registers exercise-induced transient hypoxia in both skeletal muscles and force-transmitting tendons. The fact that skeletal muscles but not tendons showed upregulation of HIF1alpha and CAIII could indicate that healthy tendons are less responsive than skeletal muscles to low levels of oxygen.
本研究的目的是使用PET/CT和缺氧选择性示踪剂（64）铜 - 二乙酰双（N（4） - 甲基硫代半卡巴腙）（ATSM），以无创方式研究大鼠骨骼肌和肌腱中与运动相关的氧合变化，并定量研究2种缺氧相关基因，即缺氧诱导因子1α（HIF1α）和碳酸酐酶III（CAIII）基因表达的伴随变化。
两组Wistar大鼠通过坐骨神经电刺激进行小腿肌肉的单腿收缩。肌肉收缩10分钟后，注射（64）铜 - ATSM，并继续收缩20分钟。在收缩后立即和1小时后对双后肢进行PET/CT检查。运动组（n = 8）仅按所述进行肌肉收缩，而另一组，运动加袖带组（n = 8），在第一次PET/CT扫描期间还经历了袖带诱导的缺氧。计算跟腱和腓肠肌的标准化摄取值（SUV），并使用实时聚合酶链反应将其与HIF1α和CAIII的基因表达相关联。
收缩后立即，与静息状态相比，（64）铜 - ATSM的摄取量显著增加，肌肉中约增加1.5倍，肌腱中约增加1.3倍。在后期PET扫描中，受刺激的肌肉和肌腱中这种显著增加持续存在，与袖带应用无关。在肌肉中，SUV与HIF1α和CAIII的基因表达显著相关，而在肌腱中未发现这种相关性。
我们发现在早期和晚期PET扫描中（64）铜 - ATSM的摄取均增强，从而支持（64）铜 - ATSM记录运动诱导的骨骼肌和力传递肌腱中短暂缺氧的可能性。骨骼肌而非肌腱中HIF1α和CAIII上调这一事实可能表明，健康的肌腱对低氧水平的反应比骨骼肌更不敏感。
