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目的:观察急性低氧暴露复氧后骨骼肌丝/苏氨酸蛋白激酶(LKB1)、AMP/ATP、结节性硬化症复合体(TSC2)、AMP依赖的蛋白激酶(AMPK)以及哺乳动物雷帕霉素靶蛋白(m TOR)信号时程变化规律,探索低氧经该信号通路下调骨骼肌蛋白合成的作用机制。方法:8周龄雄性SD大鼠分为:常氧安静组、低氧暴露即刻组、复氧1 h组、复氧2 h组、复氧6 h组和复氧12 h组。低氧暴露10 h(氧浓度13.6%)。采用HPLC检测大鼠趾长伸肌AMP、ATP含量,Western Blot测LKB1、AMPK、TSC2、m TOR磷酸化水平。结果:低氧暴露后即刻,骨骼肌AMP含量、AMP/ATP比值,LKB1、AMPK和TSC2磷酸化水平显著升高(P<0.01),同时m TOR磷酸化显著降低(P<0.01),均于复氧后6h恢复。结论:(1)低氧可以通过AMP/ATP和LKB1激活AMPK。(2)低氧可经AMPK/TSC2/m TOR通路下调m TOR活性,从而抑制骨骼肌蛋白合成。
OBJECTIVE: To observe the effects of acute hypoxia exposure on skeletal myofibrillar / threonine protein kinase (LKB1), AMP / ATP, TSC2, AMP-dependent protein kinase (AMPK) The temporal variation of mTOR signal was explored to explore the mechanism by which hypoxia down-regulated the synthesis of skeletal muscle protein by this signal pathway. Methods: Eight-week-old male SD rats were divided into two groups: normoxia group, hypoxia exposure group, reoxygenation 1 h group, reoxygenation 2 h group, reoxygenation 6 h group and reoxygenation 12 h group. Hypoxia exposure 10 h (oxygen concentration 13.6%). The content of AMP and ATP in rat extensor digitorum longus was measured by HPLC, and the phosphorylation of LKB1, AMPK, TSC2 and mTOR was detected by Western Blot. Results: Immediately after hypoxia exposure, the levels of AMP, AMP / ATP, phosphorylated LKB1, AMPK and TSC2 in skeletal muscle were significantly increased (P <0.01), while mTOR phosphorylation was significantly decreased Recovery after 6h reoxygenation. Conclusion: (1) Hypoxia can activate AMPK through AMP / ATP and LKB1. (2) Hypoxia can down-regulate mTOR activity through AMPK / TSC2 / m TOR pathway, thereby inhibiting skeletal muscle protein synthesis.