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中性粒细胞弹性蛋白酶与危重症患者急性肺损伤发生发展中的全身炎症反应综合征

Neutrophil elastase and systemic inflammatory response syndrome in the initiation and development of acute lung injury among critically ill patients.

作者信息

Fujishima Seitaro, Morisaki Hiroshi, Ishizaka Akitoshi, Kotake Yoshifumi, Miyaki Masaru, Yoh Kikuo, Sekine Kazuhiko, Sasaki Junichi, Tasaka Sadatomo, Hasegawa Naoki, Kawai Yohko, Takeda Junzo, Aikawa Naoki

机构信息

Department of Emergency and Critical Care Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.

出版信息

Biomed Pharmacother. 2008 Jun;62(5):333-8. doi: 10.1016/j.biopha.2007.07.003. Epub 2007 Jul 31.

Abstract

Critically ill patients are commonly associated with systemic inflammatory response syndrome (SIRS) and are at a greater risk of developing acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Under these conditions, large amounts of various cytokines are produced, which either directly or indirectly induce tissue injury and finally organ dysfunctions, through the activation of neutrophils and as a result of release of cytotoxic molecules, especially neutrophil elastase (NE). In the present study, we determined plasma neutrophil elastase-alpha-1 antitrypsin complex (NE-AT) and elastase digests of cross-linked fibrin (e-XDP) in critically ill patients to elucidate the significance of NE in the initiation and progression of ALI and ARDS in the presence or absence of SIRS. We found significantly increased levels of plasma NE-AT in the patients with ARDS, especially when the definition of SIRS was met. Among ALI/ARDS groups, plasma NE-AT, but not e-XDP, correlated significantly with the decrease in PaO(2)/FIO(2) ratio and the duration of ALI/ARDS. Furthermore, NE-AT, but not e-XDP, significantly increased in subgroups whose PaO(2)/FIO(2) ratio decreased by more than 20%. Such correlations and differences between the subgroups were not observed in the non-ALI patients. From these results, we speculate that NE-AT, but not e-XDP, may be predictive of progressive lung injury in the early stage of ALI and ARDS.

摘要

重症患者通常与全身炎症反应综合征(SIRS)相关,发生急性肺损伤(ALI)和急性呼吸窘迫综合征(ARDS)的风险更高。在这些情况下,会产生大量各种细胞因子,这些细胞因子通过激活中性粒细胞以及由于细胞毒性分子尤其是中性粒细胞弹性蛋白酶(NE)的释放,直接或间接诱导组织损伤并最终导致器官功能障碍。在本研究中,我们测定了重症患者血浆中的中性粒细胞弹性蛋白酶-α1抗胰蛋白酶复合物(NE-AT)和交联纤维蛋白的弹性蛋白酶消化产物(e-XDP),以阐明在存在或不存在SIRS的情况下NE在ALI和ARDS发生及进展中的意义。我们发现ARDS患者血浆NE-AT水平显著升高,尤其是在符合SIRS定义时。在ALI/ARDS组中,血浆NE-AT而非e-XDP与PaO(2)/FIO(2)比值降低及ALI/ARDS持续时间显著相关。此外,在PaO(2)/FIO(2)比值下降超过20%的亚组中,NE-AT显著升高,而e-XDP未升高。在非ALI患者中未观察到这些亚组之间的这种相关性和差异。根据这些结果,我们推测NE-AT而非e-XDP可能在ALI和ARDS早期预测进行性肺损伤。

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