Andrade F H, Anzueto A, Napier W, Levine S, Lawrence R A, Jenkinson S G, Maxwell L C
Department of Physiology, Baylor College of Medicine, Houston, Texas, USA.
Acta Physiol Scand. 1998 Feb;162(2):141-8. doi: 10.1046/j.1365-201X.1998.0265f.x.
Diaphragmatic fatigue has been associated with increased production of reactive oxygen species. Among the defenses against reactive oxygen species is the glutathione redox system. The selenium-dependent enzyme glutathione peroxidase is an important component of this system. Thus, we hypothesized that selenium deficiency would lower glutathione peroxidase activity and render the diaphragm more susceptible to a mild exertional protocol. Sprague-Dawley rats were fed a selenium-deficient or control diet for 12 weeks then divided into four experimental groups: (1) unloaded, basic diet with selenium supplementation (control); (2) unloaded, selenium-deficient diet; (3) loaded, basic diet with selenium supplementation; and (4) loaded, selenium-deficient diet. Diaphragmatic in vitro contractile properties, glutathione peroxidase activity and glutathione content were measured. During inspiratory resistive loading, the animals breathed against an inspiratory resistor at 70% of maximal airway pressure until the target pressure was not achieved for five consecutive breaths. Selenium deficiency resulted in a significant decrease in diaphragmatic glutathione peroxidase activity, without changes in total glutathione content. Neither selenium deficiency nor inspiratory resistive loading alone impaired diaphragmatic contractility. Selenium deficiency in conjunction with inspiratory resistive loading resulted in a significant decrease in diaphragmatic twitch and tetanic force, with a downward shift in the force/frequency curve. These data suggest that selenium deficiency lowers diaphragmatic glutathione peroxidase activity, and when these animals are subjected to the oxidative stress of resistive loading, there is an impairment in muscle function. We conclude that a functional glutathione peroxidase is necessary to protect the diaphragm against the effects of resistive loading.
膈肌疲劳与活性氧生成增加有关。谷胱甘肽氧化还原系统是对抗活性氧的防御机制之一。硒依赖性酶谷胱甘肽过氧化物酶是该系统的重要组成部分。因此，我们推测硒缺乏会降低谷胱甘肽过氧化物酶的活性，并使膈肌更容易受到轻度运动方案的影响。将Sprague-Dawley大鼠喂食缺硒或对照饮食12周，然后分为四个实验组：(1) 卸载，补充硒的基础饮食（对照）；(2) 卸载，缺硒饮食；(3) 加载，补充硒的基础饮食；(4) 加载，缺硒饮食。测量膈肌的体外收缩特性、谷胱甘肽过氧化物酶活性和谷胱甘肽含量。在吸气阻力负荷期间，动物以最大气道压力的70%对抗吸气阻力器呼吸，直到连续五次呼吸未达到目标压力。硒缺乏导致膈肌谷胱甘肽过氧化物酶活性显著降低，而总谷胱甘肽含量没有变化。单独的硒缺乏或吸气阻力负荷都不会损害膈肌收缩力。硒缺乏与吸气阻力负荷共同作用导致膈肌抽搐和强直力量显著降低，力/频率曲线向下移动。这些数据表明，硒缺乏会降低膈肌谷胱甘肽过氧化物酶的活性，当这些动物受到阻力负荷的氧化应激时，肌肉功能会受损。我们得出结论，功能性谷胱甘肽过氧化物酶对于保护膈肌免受阻力负荷的影响是必要的。
