Apocynin attenuates diaphragm oxidative stress and protease activation during prolonged mechanical ventilation.
Apocynin attenuates diaphragm oxidative stress and protease activation during prolonged mechanical ventilation.
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DOI：
10.1097/ccm.0b013e31819cef63
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发表时间：
2009-04
影响因子：
8.8
通讯作者：
Powers SK
中科院分区：
文献类型：
--
作者：
McClung JM;Van Gammeren D;Whidden MA;Falk DJ;Kavazis AN;Hudson MB;Gayan-Ramirez G;Decramer M;DeRuisseau KC;Powers SK
研究夹竹桃苷是否能保护机械通气（MV）期间膈肌免受消耗和氧化应激。前瞻性随机对照研究。研究实验室。成年雌性Sprague-Dawley大鼠将大鼠随机分配到五个实验组中的一个：1）急性麻醉对照，2）自主呼吸对照，3）施用烟酰胺腺嘌呤二核苷酸磷酸氧化酶抑制剂夹竹桃苷的自主呼吸对照，4）机械通气，和5）用夹竹桃苷机械通气。夹竹桃麻素减弱MV诱导的血管氧化应激、收缩功能障碍和I型、IIa型和IIb/IIx型肌纤维萎缩。夹竹桃素诱导的MV诱导的血管萎缩和收缩功能障碍的衰减与烟酰胺腺嘌呤二核苷酸磷酸氧化酶活性的小幅增加的减少以及总谷胱甘肽水平、谷胱甘肽过氧化物酶蛋白丰度的保留以及半胱氨酸蛋白酶、钙蛋白酶-1和caspase-3的活化的减少一起发生。有趣的是，独立于MV，夹竹桃麻素增加钙蛋白酶抑制剂（一种内源性钙蛋白酶抑制剂）的代谢水平。此外，用夹竹桃麻素处理培养的骨骼肌细胞（C2 C12肌管）导致钙蛋白酶抑制蛋白mRNA水平和蛋白质丰度增加。我们的研究结果表明，夹竹桃麻素的保护作用，在长期MV隔膜似乎是连接到它的功能作为一种抗氧化剂和半胱氨酸蛋白酶抑制剂钙蛋白酶抑制剂的细胞信号调节的作用。
To investigate whether apocynin protects the diaphragm from wasting and oxidative stress during mechanical ventilation (MV). Prospective, randomized, controlled study. Research laboratory. Adult female Sprague-Dawley rats. Rats were randomly assigned to one of five experimental groups: 1) acutely anesthetized control, 2) spontaneous breathing control, 3) spontaneously breathing control with administration of the nicotinamide adenine dinucleotide phosphate oxidase inhibitor, apocynin, 4) mechanically ventilated, and 5) mechanically ventilated with apocynin. Apocynin attenuated MV-induced diaphragmatic oxidative stress, contractile dysfunction, and type I, type IIa, and type IIb/IIx myofiber atrophy. The apocynin-induced attenuation of MV-induced diaphragmatic atrophy and contractile dysfunction occurred in conjunction with a reduction in the small increase in nicotinamide adenine dinucleotide phosphate oxidase activity as well as the preservation of total glutathione levels, glutathione peroxidase protein abundance, and a decrease in the activation of the cysteine proteases, calpain-1 and caspase-3. Interestingly, independent of MV, apocynin increased diaphragmatic levels of calpastatin, an endogenous calpain inhibitor. Furthermore, treatment of skeletal muscle cells in culture (C2C12 myotubes) with apocynin resulted in an increase in both calpastatin mRNA levels and protein abundance. Our results suggest that the protective effects of apocynin on the diaphragm during prolonged MV seem to be linked to both its functions as an antioxidant and role in cellular signaling regulating the cysteine protease inhibitor calpastatin.