氧化应激水平对西维来司他治疗急性肺损伤临床疗效的影响：一项电子自旋共振研究
The impact of oxidative stress levels on the clinical effectiveness of sivelestat in treating acute lung injury: an electron spin resonance study.
作者信息
Matsumoto Shigekiyo, Shingu Chihiro, Koga Hironori, Hidaka Seigo, Goto Koji, Hagiwara Satoshi, Iwasaka Hideo, Noguchi Takayuki, Yokoi Isao
机构信息
Department of Anaesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Oita, Japan.
出版信息
J Trauma. 2010 Apr;68(4):796-801. doi: 10.1097/TA.0b013e3181bb80d4.
BACKGROUND
Sivelestat, a neutrophil elastase inhibitor, has been used to treat acute lung injury (ALI) with varying levels of clinical success. Variable baseline levels of oxidative stress in patients with ALI have been proposed as one explanation for inconsistent results.
METHODS
Using a bedside electron spin resonance spectrometer, we evaluated electron spin resonance signal intensities of serum ascorbyl free radicals supplemented with dimethyl sulfoxide (AFR/DMSO) in patients with ALI.
RESULTS
We found a positive correlation between AFR/DMSO and ascorbate levels, suggesting that serum AFR/DMSO measurements may serve as a surrogate for real-time assessments of oxidative stress. Levels of AFR/DMSO in patients with ALI were significantly lower than those found in healthy controls. Stratified analyses revealed that baseline AFR/DMSO levels were significantly lower in patients with ALI who failed to respond to sivelestat compared with those who did respond.
CONCLUSIONS
Our results suggest that the clinical efficacy of sivelestat is dependent on baseline oxidative stress levels.
背景
西维来司他是一种中性粒细胞弹性蛋白酶抑制剂，已被用于治疗急性肺损伤（ALI），临床疗效各异。急性肺损伤患者氧化应激的基线水平不同被认为是导致结果不一致的原因之一。
方法
我们使用床边电子自旋共振光谱仪，评估了急性肺损伤患者血清抗坏血酸自由基补充二甲基亚砜（AFR/DMSO）后的电子自旋共振信号强度。
结果
我们发现AFR/DMSO与抗坏血酸盐水平呈正相关，这表明血清AFR/DMSO测量可作为氧化应激实时评估的替代指标。急性肺损伤患者的AFR/DMSO水平显著低于健康对照组。分层分析显示，与有反应的急性肺损伤患者相比，对西维来司他无反应的患者基线AFR/DMSO水平显著更低。
结论
我们的结果表明，西维来司他的临床疗效取决于基线氧化应激水平。
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