Morales C F, Anzueto A, Andrade F, Brassard J, Levine S M, Maxwell L C, Lawrence R A, Jenkinson S G
Division of Pulmonary Diseases/Critical Care Medicine, University of Texas Health Science Center at San Antonio 78284-7885.
Am J Respir Crit Care Med. 1994 Apr;149(4 Pt 1):915-9. doi: 10.1164/ajrccm.149.4.7908245.
Activation of the glutathione (GSH) redox cycle with production of glutathione disulfide (GSSG) has been shown to occur in the diaphragm during inspiratory resistive loading (RB). Buthionine sulfoximine (BSO) lowers tissue GSH by irreversibly inhibiting the rate-limiting synthesis enzyme gamma-glutamylcysteine synthetase. We investigated the effects of BSO on rat diaphragm function, both at rest and after a period of RB. Rats in the RB groups underwent inspiratory RB until they were unable to sustain 70% of their maximal airway pressure. A portion of the diaphragm was analyzed for GSH and GSSG levels, and measurements of in vitro contractile properties included contraction times, maximal tetanic tension (Po), maximal twitch tension (Pt), and force frequency curves. BSO treatment produced a profound depletion of diaphragmatic GSH. Neither BSO nor RB alone significantly altered diaphragm contractile properties at this load of RB. But, in BSO-RB rats, there was a significant decrease in Pt, Po, and tetanic tension at all frequencies of stimulation compared with those in other groups. These data reveal that animals treated with BSO followed by inspiratory resistive loading exhibit marked diaphragm impairment, suggesting that GSH may play an important role in protecting the diaphragm from the stress induced by this resistive breathing protocol.
在吸气性阻力负荷（RB）期间，膈肌中已显示会发生谷胱甘肽（GSH）氧化还原循环的激活并产生谷胱甘肽二硫化物（GSSG）。丁硫氨酸亚砜胺（BSO）通过不可逆地抑制限速合成酶γ-谷氨酰半胱氨酸合成酶来降低组织中的GSH。我们研究了BSO对大鼠膈肌功能的影响，包括在静息状态下以及在一段RB之后的影响。RB组的大鼠进行吸气性RB，直到它们无法维持其最大气道压力的70%。分析膈肌的一部分以检测GSH和GSSG水平，体外收缩特性的测量包括收缩时间、最大强直张力（Po）、最大抽搐张力（Pt）和力频率曲线。BSO处理导致膈肌GSH显著耗竭。在这种RB负荷下，单独使用BSO或RB均未显著改变膈肌的收缩特性。但是，与其他组相比，在BSO-RB大鼠中，在所有刺激频率下Pt、Po和强直张力均显著降低。这些数据表明，先用BSO处理然后进行吸气性阻力负荷的动物表现出明显的膈肌损伤，这表明GSH可能在保护膈肌免受这种阻力呼吸方案诱导的应激方面发挥重要作用。
