Mechanical ventilation-induced diaphragmatic atrophy is associated with oxidative injury and increased proteolytic activity
Mechanical ventilation-induced diaphragmatic atrophy is associated with oxidative injury and increased proteolytic activity
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DOI：
10.1164/rccm.200202-088oc
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发表时间：
2002-11-15
影响因子：
24.7
通讯作者：
Powers, SK
中科院分区：
文献类型：
--
作者：
Shanely, RA;Zergeroglu, MA;Powers, SK
延长机械通气（MV）导致膈肌最大力产生减少和膈肌萎缩。为了研究MV诱导横膈膜萎缩的机制，我们验证了一个假设，即控制MV会导致横膈膜蛋白氧化，并由于蛋白酶活性升高而增加横膈膜蛋白水解。此外，我们假设MV会导致所有膈肌纤维类型的萎缩。机械通气动物麻醉，气管造口，21% O-2通气18小时。MV导致膈肌肌原纤维蛋白和所有肌纤维类型（即I、IIa、IId/x和IIb）的横截面积降低（p < 0.05）。此外，MV促进了横膈膜蛋白降解的增加（p < 0.05），并提高了calpain和20S蛋白酶体的活性（p < 0.05）。最后，MV还与蛋白氧化和脂质过氧化升高相关（p < 0.05）。这些数据支持了MV与所有膈纤维类型萎缩、膈蛋白酶活性增加和膈氧化应激增强有关的假设。
Prolonged mechanical ventilation (MV) results in reduced diaphragmatic maximal force production and diaphragmatic atrophy. To investigate the mechanisms responsible for MV-induced diaphragmatic atrophy, we tested the hypothesis that controlled MV results in oxidation of diaphragmatic proteins and increased diaphragmatic proteolysis due to elevated protease activity. Further, we postulated that MV would result in atrophy of all diaphragmatic muscle fiber types. Mechanically ventilated animals were anesthetized, tracheostomized, and ventilated with 21% O-2 for 18 hours. MV resulted in a decrease (p < 0.05) in diaphragmatic myofibrillar protein and the cross-sectional area of all muscle fiber types (i.e., I, IIa, IId/x, and IIb). Further, MV promoted an increase (p < 0.05) in diaphragmatic protein degradation along with elevated (p < 0.05) calpain and 20S proteasome activity. Finally, MV was also associated with a rise (p < 0.05) in both protein oxidation and lipid peroxidation. These data support the hypothesis that MV is associated with atrophy of all diaphragmatic fiber types, increased diaphragmatic protease activity, and augmented diaphragmatic oxidative stress.