Wang Chia-Ti, Lin Hung-Jung, Cheng Bor-Chih, Lin Mao-Tsun, Chang Ching-Ping
Department of Emergency Medicine, Chi Mei Medical Center, Tainan, Taiwan.
Department of Emergency Medicine, Chi Mei Medical Center, Tainan, Taiwan; Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan.
J Formos Med Assoc. 2015 Apr;114(4):328-38. doi: 10.1016/j.jfma.2012.11.015. Epub 2013 Jan 11.
BACKGROUND/PURPOSE: The primary goal of this study was to test whether high-altitude exposure (HAE: 0.9% O(2) at 0.47 ATA for 24 hours) was capable of increasing the systemic inflammatory markers as well as the toxic organ injury indicators in rats, with a secondary goal to test whether preinduction of heat shock protein (HSP) 70 by hypobaric hypoxia preconditioning (HHP: 18.3% O(2) at 0.66 ATA for 5 h/day on 5 days consecutively for 2 weeks) attenuated the proposed increased serum levels of both the systemic inflammatory markers and the toxic organ injury indicators.
Rats were assigned to: (1) non-HHP (21% O(2) at 1.0 ATA)+non-HAE (21% O(2) at 1.0 ATA) group; (2) non-HHP+HAE group; (3) HHP+non-HAE group; (4) HHP+HAE group; and (5) HHP+HSP70 antibodies (Ab)+HAE group. For the HSP70Ab group, a neutralizing HSP70Ab was injected intravenously at 24 hours prior to HAE. All the physiological and biochemical parameters were obtained at the end of HAE or the equivalent time period of non-HAE. Blood samples were obtained for determination of both the systemic inflammatory markers (e.g., serum tumor necrosis factor-α, interleukin-1β, E-selectin, intercellular adhesion molecule-1, and liver myeloperoxidase activity) and the toxic organ injury indicators (e.g., nitric oxide metabolites, 2,3-dihydroxybenzoic acid, and lactate dehydrogenase).
HHP, in addition to inducing overexpression of tissue HSP70, significantly attenuated the HAE-induced hypotension, bradycardia, hypoxia, acidosis, and increased tissue levels of both the systemic inflammatory markers and the toxic organ injury indicators. The beneficial effects of HHP in inducing tissue overexpression of HSP70 as well as in preventing the HAE-induced increased levels of the systemic inflammatory markers and the toxic organ injury indicators could be significantly reduced by HSP70Ab preconditioning.
These results suggest that HHP may downgrade both the systemic inflammatory markers and the toxic organ injury indicators in HAE by upregulating tissue HSP70.
背景/目的：本研究的主要目标是测试高海拔暴露（HAE：在0.47ATA下0.9%氧气，持续24小时）是否能够增加大鼠体内的全身炎症标志物以及毒性器官损伤指标，次要目标是测试低压缺氧预处理（HHP：在0.66ATA下18.3%氧气，连续5天每天5小时，共2周）预先诱导热休克蛋白（HSP）70是否能减弱全身炎症标志物和毒性器官损伤指标血清水平的升高。
将大鼠分为：（1）非HHP（1.0ATA下21%氧气）+非HAE（1.0ATA下21%氧气）组；（2）非HHP+HAE组；（3）HHP+非HAE组；（4）HHP+HAE组；（5）HHP+HSP70抗体（Ab）+HAE组。对于HSP70Ab组，在HAE前24小时静脉注射中和性HSP70Ab。在HAE结束时或非HAE的等效时间段获取所有生理和生化参数。采集血样以测定全身炎症标志物（如血清肿瘤坏死因子-α、白细胞介素-1β、E-选择素、细胞间黏附分子-1和肝脏髓过氧化物酶活性）和毒性器官损伤指标（如一氧化氮代谢产物、2,3-二羟基苯甲酸和乳酸脱氢酶）。
HHP除了诱导组织HSP70过表达外，还显著减弱了HAE诱导的低血压、心动过缓、缺氧、酸中毒以及全身炎症标志物和毒性器官损伤指标的组织水平升高。HSP70Ab预处理可显著降低HHP在诱导组织HSP70过表达以及预防HAE诱导的全身炎症标志物和毒性器官损伤指标水平升高方面的有益作用。
这些结果表明，HHP可能通过上调组织HSP70来降低HAE中的全身炎症标志物和毒性器官损伤指标。
