The effect of heat stress on signal transduction during the recovery from skeletal muscle atrophy induced by hindlimb-unweighted

最近有报道称Akt/mTOR/p70^<S6K>/S6和钙调磷酸酶信号通路是骨骼肌肥大的重要调节因子。研究表明，热应激可加速后肢减重引起的骨骼肌萎缩的恢复。然而，热应激对萎缩肌肉的促进作用的机制尚不清楚。在本研究中，我们研究了Akt和钙调磷酸酶信号通路在热作用下萎缩骨骼肌恢复中的作用及其最佳暴露时间。将Wistar雄性大鼠（8周龄）分为4组：对照组（Con）、后肢称重组（HLU）、后肢称重后热应激15 （heat 15）和30 (heat 30) min。HLU组、Heat 15组和Heat 30组后肢减重10 d。称重释放后立即将热组麻醉下浸入42℃热水中。分别于第0、3、10天解剖比目鱼肌。各组HLU和Heat 15的肌重/体重比均显著高于第0天。在10 d恢复期，热30的肌原纤维含量显著低于对照组。肌肉再负荷0 d后，Heat 15组的phospho-mTOR表达显著高于其他各组。恢复期3 d后的磷酸化-S6核糖体水平依次为：Heat 15、HLU、Heat 30和con。这些结果表明，热应激促进萎缩骨骼肌恢复的部分途径是Akt/mTOR/p70^<S6K>/S6信号通路，且存在促进其恢复的最佳暴露时间。

It has been recently reported that Akt/mTOR/p70^<S6K>/S6 and calcineurin signaling pathways are a crucial regulator of skeletal muscle hypertrophy. We have showed that the heat stress accelerates the recovery from skeletal muscle atrophy induced by hindlimb unweighting. However, the mechanism responsible for the promoting effects of heat stress on atrophied muscles remains unclear. In this study, we investigated the role of the Akt and calcineurin signaling pathway in the recovery of the atrophied skeletal muscle with heat and its optimum exposure time. Wistar strain male rats (8-week-old) were divided into four groups : control (Con), hindlimb unweighting (HLU), heat stress for 15 (Heat 15) and 30 (Heat 30) min after hindlimb unweighting. HLU, Heat 15 and Heat 30 groups were subjected to hindlimb unweighting for 10 days. Immediately after release from unweighting, heat groups were immersed into hot water (42℃) under anesthesia. After 0, 3 and 10 days, soleus muscles were dissected. Muscle weight-to-body weight ratios of HLU and Heat 15 were significantly higher than 0 day in each group. The myofibrillar content of Heat 30 was significantly lower than Con at 10 day recovery period. The expression of phospho-mTOR in Heat 15 was significantly higher than the other groups after 0 days of muscle reloding. Phospho-S6 ribosomal levels after 3 day recovery period were significantly greater in the order : Heat 15, HLU, Heat 30 and Con. These results suggest that the heat stress promotes the recovery of atrophied skeletal muscle in part via Akt/mTOR/p70^<S6K>/S6 signaling pathway and the optimum exposure time for its promotion exist.