Abstract 120: Response of Rat Lung Tissue to Short-Term Hyperoxia: A Proteomic Approach
Introduction: Hyperoxia after resuscitation results in a poor neurological outcome and leads to deleterious consequences for brain, heart and lungs. It is well known that hyperoxia increases the risk of tissue toxicity and inflammation by generating radical oxygen species. Nevertheless sufficient oxygenation is vitally important to avoid hypoxia in emergency medicine. However, the impact of hyperoxia on the expression of lung proteins has not yet been evaluated in detail. We assessed the hypothesis that even short term hyperoxia leads to alterations of protein expression in rat lung.
Methods: After approval from the local ethics committee for animal studies, n=36 wistar rats were randomized into six different groups: three groups with normobaric hyperoxia (NH) and three groups with normobaric normoxia (NN). Normobaric hyperoxia was obtained by exposure to 100 % oxygen for three hours in contrast to normobaric normoxia which was obtained by exposure to room air. Lungs were removed immediately after the end of the experiments (NH0 / NN0 groups), after three days (NH3 / NN3) or after seven days (NH7 / NN7). Lung lysates were analyzed by two-dimensional gel electrophoresis followed by subsequent identification of protein expression by mass spectroscopy. Statistical analysis was performed with Delta 2D (DECODON, Germany). Biological functions of differential regulated proteins (ANOVA, Bonferroni correction, p<0.01) were studied using functional network analysis (Ingenuity Pathways Analysis, IPA).
Results: PaO2 was significantly increased 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 changed: 2 proteins were up-regulated (i.e. Interferon-induced protein [Ifit3]) and 12 proteins were down-regulated (i.e. Thiol-specific antioxidant-like protein [Thioap]). A correlation between protein regulation and cellular outcome was identified by IPA.
Conclusion: Even though hyperoxia was comparatively short, significant alterations in protein expression could be detected up to seven days after hyperoxia in lung tissue. Therefore even persistent protein alterations are possible due to a pulmonary cell injury.
- © 2011 by American Heart Association, Inc.