High-altitude pulmonary edema can be prevented by heat shock protein 70-mediated hyperbaric oxygen preconditioning

摘要

The primary goal of this study was to test whether high-altitude exposure (HAE of 9.7% O_2 at 0.47 absolute atmosphere [ATA] for 3 days) was capable of increasing lung edema, neutrophil, and hemorrhage scores as well as decreasing lung levels of both aquaporin 1 (AQP1) and AQP5 proteins and messenger RNA (mRNA) expression in rats, with a secondary goal to test whether a preinduction of heat shock protein 70 (HSP70) by hyperbaric oxygen preconditioning (HBO_2P of 100% O_2 at 2.0 ATA for 1 hour per day for 5 consecutive days) attenuated the HAE-induced increased lung injury scores and decreased lung AQP1 and AQP5 protein and mRNA expressions.Rats were assigned to (1) non-HBO_2P (21% O_2 at 1.0 ATA) + non-HAE (21% O_2 at 1.0 ATA) group; (2) non-HBO_2P + HAE group; (3) HBO_2P + HAE group; and HBO_2P + HSP70 antibodies (Ab) + HAE group. For the HSP70 Ab group, a neutralizing HSP70 Ab was injected intravenously at 24 hours before HAE. All the physiologic and biochemical parameters were obtained at the end of HAE or the equivalent period of non-HAE. The cardiovascular and blood gas parameters were monitored for all experiments. Bronchoalveolar lavage (BAL) was performed to determine proinflammatory cytokines (interleukin 6, interleukin 1P, and tumor necrosis factor a). Parts of the lung were excised for myeloperoxidase activity measurement, whereas the rest was collected for lung damage score assessments. AQP1 and AQP5 protein and mRAN expressions were also determined in the lung tissues.