Xanthine oxidase contributes to mechanical ventilation-induced diaphragmatic oxidative stress and contractile dysfunction
Xanthine oxidase contributes to mechanical ventilation-induced diaphragmatic oxidative stress and contractile dysfunction
复制标题
DOI：
10.1152/japplphysiol.91106.2008
复制
发表时间：
2009-02-01
影响因子：
3.3
通讯作者：
Powers, Scott K.
中科院分区：
文献类型：
--
作者：
Whidden, Melissa A.;McClung, Joseph M.;Powers, Scott K.
Whidden MA，McClung JM，Falk DJ，哈德逊MB，Smuder AJ，纳尔逊WB，Powers SK.黄嘌呤氧化酶有助于机械通气诱导的动脉氧化应激和收缩功能障碍。J Appl Physiol 106：385-394，2009.首次发表于2008年10月30日; doi：10.1152/japplphysiol.91106.2008。由呼吸肌收缩功能障碍和萎缩引起的呼吸肌无力被认为是与长期机械通气（MV）相关的脱机困难的原因。虽然很明显，氧化损伤有助于MV诱导的膈肌无力，但MV期间膈肌中氧化剂的来源仍不清楚。这些实验测试的假设，黄嘌呤氧化酶（XO）有助于MV诱导的氧化剂在大鼠膈肌的生产和oxypurinol，XO抑制剂，将减弱MV诱导的血管氧化应激，收缩功能障碍，和萎缩。将成年雌性Sprague-Dawley大鼠随机分配到六个实验组之一：1）对照组，2）奥昔嘌呤醇对照组，3）MV 12 h组，4）MV 12 h组（奥昔嘌呤醇），5）MV 18 h组，或6）MV 18 h组（奥昔嘌呤醇）。XO活性显着升高，在隔膜后MV，和oxypurinol管理抑制这种活动，并提供保护MV诱导的氧化应激和收缩功能障碍。具体而言，奥昔嘌呤醇治疗部分衰减蛋白质氧化和脂质过氧化反应在隔膜在MV。此外，在刺激频率>60 Hz时，XO抑制可延缓MV诱导的横隔膜收缩功能障碍。总的来说，这些结果表明，XO产生的氧化剂有助于MV诱导的氧化损伤和膈肌收缩功能障碍。尽管如此，XO抑制完全防止MV诱导的血管氧化损伤的失败表明，在延长MV期间，其他氧化剂产生来源在隔膜中是活跃的。
Whidden MA, McClung JM, Falk DJ, Hudson MB, Smuder AJ, Nelson WB, Powers SK. Xanthine oxidase contributes to mechanical ventilation-induced diaphragmatic oxidative stress and contractile dysfunction. J Appl Physiol 106: 385-394, 2009. First published October 30, 2008; doi: 10.1152/japplphysiol.91106.2008.-Respiratory muscle weakness resulting from both diaphragmatic contractile dysfunction and atrophy has been hypothesized to contribute to the weaning difficulties associated with prolonged mechanical ventilation (MV). While it is clear that oxidative injury contributes to MV-induced diaphragmatic weakness, the source(s) of oxidants in the diaphragm during MV remain unknown. These experiments tested the hypothesis that xanthine oxidase (XO) contributes to MV-induced oxidant production in the rat diaphragm and that oxypurinol, a XO inhibitor, would attenuate MV-induced diaphragmatic oxidative stress, contractile dysfunction, and atrophy. Adult female Sprague-Dawley rats were randomly assigned to one of six experimental groups: 1) control, 2) control with oxypurinol, 3) 12 h of MV, 4) 12 h of MV with oxypurinol, 5) 18 h of MV, or 6) 18 h of MV with oxypurinol. XO activity was significantly elevated in the diaphragm after MV, and oxypurinol administration inhibited this activity and provided protection against MV-induced oxidative stress and contractile dysfunction. Specifically, oxypurinol treatment partially attenuated both protein oxidation and lipid peroxidation in the diaphragm during MV. Further, XO inhibition retarded MV-induced diaphragmatic contractile dysfunction at stimulation frequencies >60 Hz. Collectively, these results suggest that oxidant production by XO contributes to MV-induced oxidative injury and contractile dysfunction in the diaphragm. Nonetheless, the failure of XO inhibition to completely prevent MV-induced diaphragmatic oxidative damage suggests that other sources of oxidant production are active in the diaphragm during prolonged MV.