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骨骼肌线粒体解耦联蛋白3(uncoupling protein3,UCP3)在低氧时的生理作用尚不清楚。本研究观察了大鼠在耐力训练前后,模拟急性高原低氧各时间点的骨骼肌线粒体UCP3mRNA和蛋白表达、线粒体呼吸功能、活性氧(reactive oxygen species,ROS)产生速率以及锰超氧化物歧化酶(manganese superoxide dismutase,MnSOD)表达和活性的变化。急性低氧导致线粒体一系列生物能学功能障碍。未训练大鼠UCP3蛋白在4h时比静息时升高了60%,而MnSOD蛋白含量及活性在低氧暴露过程中无显著变化;UCP3蛋白上调通过降低电子传递链耦联程度抑制O2?-产生,但同时降低了ATP合成效率。耐力训练显著抑制急性低氧诱导的骨骼肌UCP3蛋白上调(67%vs42%)。训练组大鼠的ROS产生速率在低氧2h、4h和6h时显著低于未训练组;MnSOD蛋白含量及活性分别较未训练组提高了50%和34%。训练组大鼠MnSOD上调可增加线粒体对ROS的耐受力,进而抑制UCP3蛋白表达,从而提高氧化磷酸化效率。急性低氧中,未训练组大鼠呼吸控制比(respiratory control ratio,RCR)和磷氧比(ADP to oxygen consumption ratio,P/O)显著降低,而训练组RCR和P/O保持相对稳定。以上结果提示:(1)模拟急性高原低氧可诱导UCP3 mRNA及蛋白表达升高,从而降低升高了的线粒体膜电位(Δψ),使ROS的产生减少;(2)耐力训练可抑制低氧诱导的UCP3表达上调,提高ROS酶学清除能力,从而提高线粒体氧化磷酸化效率。
The physiological role of uncoupling protein3 (UCP3) in hypoxia is unclear. In this study, we observed the mRNA and protein expression of skeletal muscle mitochondria UCP3, mitochondrial respiratory function, the production rate of reactive oxygen species (ROS) and the activity of manganese superoxide dismutase (SOD) in rats before and after endurance training. (manganese superoxide dismutase, MnSOD) expression and activity changes. Acute hypoxia leads to a series of mitochondrial bioenergetic dysfunctions. UCP3 protein in untrained rats increased by 60% at 4h, while MnSOD protein content and activity did not change significantly during hypoxia exposure. UCP3 protein up-regulated by reducing the degree of electron transfer chain coupling to inhibit O2- But at the same time reduced the efficiency of ATP synthesis. Endurance training significantly inhibited the upregulation of skeletal muscle UCP3 protein induced by acute hypoxia (67% vs42%). The ROS production rate in training group was significantly lower than that in non-training group at 2h, 4h and 6h after hypoxia; MnSOD protein content and activity were increased by 50% and 34% respectively compared with untreated group. Up-regulation of MnSOD in training group increased the tolerance of mitochondria to ROS, and then inhibited the expression of UCP3 protein, thereby increasing the oxidative phosphorylation efficiency. In acute hypoxia, the respiratory control ratio (RCR) and the P / O ratio of the untreated group were significantly decreased, while the RCR and P / O of the training group remained relatively stable. The above results suggest that: (1) Simulated acute hypoxia induced UCP3 mRNA and protein expression increased, thereby reducing the elevated mitochondrial membrane potential (Δψ), so that the production of ROS decreased; (2) Endurance training can inhibit hypoxia Induced UCP3 upregulation, increase ROS enzymatic clearance, thereby enhancing mitochondrial oxidative phosphorylation efficiency.