过刊浏览

耐力训练抑制急性低氧时骨骼肌线粒体生物能学变化:ROS和UCP3的作用

薄海, 王义和, 李海英, 赵娟, 张红英, 佟长青

武警医学院生理学与病理生理学教研室.天津 300162；武警医学院机能中心教研室.天津 300162；武警总医院科训科.北京 100039

摘要

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。该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O_(2)~(.-)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% vs 42%)。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(#DELTA##psi#),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。

关键词： 骨骼肌线粒体; 耐力训练; 低氧; 解耦联蛋白3; 活性氧

Endurance training attenuates the bioenergetics alterations of rat skeletal muscle mitochondria submitted to acute hypoxia:Role of ROS and UCP3

BO Hai, Wang Yihe, Li Haiying, Zhao Juan, Zhang Hongying, Tong Changqing

Department of Physiology and Pathophysiology,Medical College of Chinese People's Armed Police Force.Tianjin 300162；China；Science and Research Department,General Hospital of Chinese People's Armed Police Force.Beijing 100039

Abstract

The physiological significance of skeletal muscle mitochondrial uncoupling protein 3(UCP3) in hypoxia is elusive.In the current study,UCP3 mRNA and protein expressions were investigated along with mitochondrial respiratory function,reactive oxygen species(ROS) generation,as well as manganese superoxide dismutase(MnSOD) expression in rat skeletal muscle with or without endurance training after an acute and severe hypobaric hypoxia exposure for different time.Acute hypoxia induced a series of impairments in skeletal muscle mitochondrial bioenergetics.In untrained rats,UCP3 protein content increased by 60% above resting level at 4 h hypoxia,whereas MnSOD protein content and activity were unaltered.UCP3 upregulation increased mitochondrial uncoupling respiration thus reducing O_(2)~(.-) generation,but inevitably decreased ATP production.Training decreased acute hypoxia-induced upregulation of UCP3 protein(67% vs 42%) in rat skeletal muscle.ROS production in trained rats also showed a dramatic decrease at 2 h,4 h and 6 h,respectively,compared with that in untrained rats.MnSOD protein contents and activities were significantly(50% and 34%) higher in trained than those in untrained rats.Training adaptation of MnSOD may enhance the mitochon-drial tolerance to ROS production,and reduce UCP3 activation during severe hypoxia,thus maintaining the efficiency of oxidative phosphorylation.In trained rats,mitochondrial respiratory control(RCR) and P/O ratios were maintained relatively constant despite severe hypoxia,whereas in untrained rats RCR and P/O ratios were significantly decreased.These results indicate that(1) UCP3 mRNA and protein expression in rat skeletal muscle are upregulated during acute and severe hypobaric hypoxia,which may reduce the increased cross-membrane potential (#DELTA##psi#) and thus ROS production;(2) Endurance training can blunt hypoxia-induced UCP3 upregulation,and improve mitochondrial efficiency of oxidative phosphorylation due to increased removal of ROS.

Key words: muscle mitochondria;training;Hypoxia;uncoupling protein 3;Reactive oxygen species

收稿日期：　　录用日期：

通讯作者：　　E-mail:

引用本文：

薄海, 王义和, 李海英, 赵娟, 张红英, 佟长青. 耐力训练抑制急性低氧时骨骼肌线粒体生物能学变化:ROS和UCP3的作用[J]. 生理学报 2008; 60 (6): 767-776.

BO Hai, Wang Yihe, Li Haiying, Zhao Juan, Zhang Hongying, Tong Changqing. Endurance training attenuates the bioenergetics alterations of rat skeletal muscle mitochondria submitted to acute hypoxia:Role of ROS and UCP3. Acta Physiol Sin 2008; 60 (6): 767-776 (in Chinese with English abstract).