Mechanical ventilation promotes redox status alterations in the diaphragm
Mechanical ventilation promotes redox status alterations in the diaphragm
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DOI：
10.1152/japplphysiol.00104.2006
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发表时间：
2006-10-01
影响因子：
3.3
通讯作者：
Powers, S. K.
中科院分区：
文献类型：
--
作者：
Falk, D. J.;DeRuisseau, K. C.;Powers, S. K.
氧化应激是长时间受控机械通气（MV）期间膈肌萎缩和收缩功能障碍的重要介质。迄今为止，与MV对代谢性氧化还原状态的影响相关的具体细节仍然未知。为了填补这一空白，我们测试了这一假设，MV诱导的细胞内氧化应激是一个在细胞内氧化剂的生产与抗氧化剂缓冲能力的降低结合在一起的结果。成年大鼠被分配到两个实验组之一：1）对照组或2）MV 12 h组。与对照组相比，MV动物的横膈膜表现出氧化剂产生增加，总抗氧化能力降低，谷胱甘肽水平降低。血红素氧合酶-1（HO-1）的mRNA和蛋白水平增加（23.0和5.1倍，分别）后MV。硫氧还蛋白还原酶-1和锰超氧化物歧化酶的mRNA水平也增加了隔膜MV（2.4和1.6倍，分别），虽然没有变化的蛋白质水平检测。此外，铜锌超氧化物歧化酶和谷胱甘肽过氧化物酶的mRNA没有改变后MV，虽然蛋白质含量下降-1.3-和-1.7-倍，分别。我们的结论是，MV促进增加氧化剂的产生和隔膜中的关键抗氧化剂防御的损害;总的来说，这些变化有助于MV诱导的氧化应激在这个关键的吸气肌肉。
Oxidative stress is an important mediator of diaphragm muscle atrophy and contractile dysfunction during prolonged periods of controlled mechanical ventilation (MV). To date, specific details related to the impact of MV on diaphragmatic redox status remain unknown. To fill this void, we tested the hypothesis that MV-induced diaphragmatic oxidative stress is the consequence of both an elevation in intracellular oxidant production in conjunction with a decrease in the antioxidant buffering capacity. Adult rats were assigned to one of two experimental groups: 1) control or 2) 12 h of MV. Compared with controls, diaphragms from MV animals demonstrated increased oxidant production, diminished total antioxidant capacity, and decreased glutathione levels. Heme oxygenase-1 (HO-1) mRNA and protein levels increased (23.0 and 5.1-fold, respectively) following MV. Thioredoxin reductase-1 and manganese superoxide dismutase mRNA levels were also increased in the diaphragm following MV (2.4- and 1.6-fold, respectively), although no change was detected in the levels of either protein. Furthermore, copper-zinc superoxide dismutase and glutathione peroxidase mRNA were not altered following MV, although protein content decreased -1.3- and -1.7-fold, respectively. We conclude that MV promotes increased oxidant production and impairment of key antioxidant defenses in the diaphragm; collectively, these changes contribute to the MV-induced oxidative stress in this key inspiratory muscle.