Department of Anesthesiology and Intensive Care Medicine, University Hospital of Cologne, 50937, Cologne, Germany,
Mol Cell Biochem. 2013 Nov;383(1-2):231-42. doi: 10.1007/s11010-013-1771-y. Epub 2013 Aug 11.
An inspiratory oxygen fraction of 1.0 is often required to avoid hypoxia both in many pre- and in-hospital situations. On the other hand, hyperoxia may lead to deleterious consequences (cell growth inhibition, inflammation, and apoptosis) for numerous tissues including the lung. Whereas clinical effects of hyperoxic lung injury are well known, its impact on the expression of lung proteins has not yet been evaluated sufficiently. The aim of this study was to analyze time-dependent alterations of protein expression in rat lung tissue after short-term normobaric hyperoxia (NH). After approval of the local ethics committee for animal research, N = 36 Wistar rats were randomized into six different groups: three groups with NH with exposure to 100 % oxygen for 3 h and three groups with normobaric normoxia (NN) with exposure to room air (21 % oxygen). After the end of the experiments, lungs were removed immediately (NH0 and NN0), after 3 days (NH3 and NN3) and after 7 days (NH7 and NN7). Lung lysates were analyzed by two-dimensional gel electrophoresis (2D-GE) followed by peptide mass fingerprinting using mass spectrometry. Statistical analysis was performed with Delta 2D (DECODON GmbH, Greifswald, Germany; ANOVA, Bonferroni correction, p < 0.01). Biological functions of differential regulated proteins were studied using functional network analysis (Ingenuity Pathways Analysis, IPA). pO2 was significantly higher in NH-groups compared to NN-groups (581 ± 28 vs. 98 ± 12 mmHg; p < 0.01), all other physiological parameters did not differ. Expression of 14 proteins were significantly altered: two proteins were up-regulated and 12 proteins were down-regulated. Even though NH was comparatively short termed, significant alterations in lung protein expression could be demonstrated up to 7 days after hyperoxia. The identified proteins indicate an association with cell growth inhibition, regulation of apoptosis, and approval of structural cell integrity.
在许多术前和住院期间的情况下，通常需要吸入 1.0 的氧分数来避免缺氧。另一方面，高氧可能导致包括肺在内的许多组织产生有害后果（细胞生长抑制、炎症和细胞凋亡）。虽然高氧性肺损伤的临床效果众所周知，但它对肺蛋白表达的影响尚未得到充分评估。本研究的目的是分析短期常压高氧（NH）后大鼠肺组织中蛋白质表达的时间依赖性变化。在获得当地动物研究伦理委员会的批准后，将 N = 36 只 Wistar 大鼠随机分为六组：三组 NH 组，暴露于 100%氧气 3 小时，三组 NN 组，暴露于室内空气（21%氧气）。实验结束后，立即取出肺（NH0 和 NN0）、3 天后（NH3 和 NN3）和 7 天后（NH7 和 NN7）。通过二维凝胶电泳（2D-GE）分析肺裂解物，然后使用质谱进行肽质量指纹图谱分析。使用 Delta 2D（DECODON GmbH，Greifswald，德国；ANOVA，Bonferroni 校正，p < 0.01）进行统计分析。使用功能网络分析（Ingenuity Pathways Analysis，IPA）研究差异调节蛋白的生物学功能。NH 组的 pO2 明显高于 NN 组（581 ± 28 与 98 ± 12 mmHg；p < 0.01），所有其他生理参数无差异。有 14 种蛋白质的表达明显改变：两种蛋白质上调，12 种蛋白质下调。尽管 NH 相对短暂，但在高氧后 7 天内仍能证明肺蛋白表达的显著改变。鉴定出的蛋白质表明与细胞生长抑制、细胞凋亡调节和结构细胞完整性的认可有关。
