Department of NeuroTrauma, Naval Medical Research Center, 503 Robert Grant Ave., Silver Spring, MD 20910-7500, USA.
J Appl Physiol (1985). 2011 Oct;111(4):1007-13. doi: 10.1152/japplphysiol.01402.2010. Epub 2011 Jul 14.
Previous studies demonstrated that animals exposed to repeated compression-decompression stress acclimated (i.e., developed reduced susceptibility) to rapid decompression. This study endeavored to characterize inflammatory and stress-related gene expression and signal transduction associated with acclimation to rapid decompression. Rats were divided into four groups: 1) control-sham: pressure naïve rats; 2) acclimation-sham: nine acclimation dives [70 feet seawater (fsw), 30 min]; 3) control-dive: test dive only (175 fsw, 60 min); and 4) acclimation-dive: nine acclimation dives and a test dive. After the test dive, rats were observed for decompression sickness (DCS). Expression of 13 inflammatory and stress-related genes and Akt (or PKB, a serine/threonine protein kinase) and MAPK phosphorylation of lung tissue were examined. The expression of immediate early gene/transcription factor early growth response gene 1 (Egr-1) was observed in both control and acclimation animals with DCS but not in animals without DCS. Increased Egr-1 in control-dive animals with DCS was significantly greater than in acclimation-dive animals with DCS. TNF-α, IL-1β, IL-6, and IL-10 were significantly elevated in control-DCS animals. Acclimation-DCS animals had increased TNF-α, but there was no change in IL-1β, IL-6, and IL-10. High levels of Akt phosphorylation were observed in lungs of acclimation-sham, acclimation-dive, and control-dive animals; phosphorylated ERK1/2 was only observed in animals with DCS. This study suggests that activation of ERK1/2 and upregulation of Egr-1 and its target cytokine genes by rapid decompression may play a role in the initiation and progression of DCS. It may be that the downregulated expression of these genes in animals with DCS is associated with previous exposure to repeated compression-decompression cycles. This study represents an initial step toward understanding the molecular mechanisms associated with acclimation to decompression.
先前的研究表明，反复经受压缩-减压应激的动物适应了（即，对快速减压的敏感性降低）。本研究旨在描述与快速减压适应相关的炎症和应激相关基因表达和信号转导。将大鼠分为四组：1）对照-假潜水组：未接触过压力的大鼠；2）适应-假潜水组：进行 9 次适应潜水[70 英尺海水（fsw），30 分钟]；3）对照潜水组：仅进行一次测试潜水（175 fsw，60 分钟）；4）适应潜水组：进行 9 次适应潜水和一次测试潜水。测试潜水后，观察大鼠是否出现减压病（DCS）。检测了肺组织中 13 种炎症和应激相关基因以及 Akt（或 PKB，丝氨酸/苏氨酸蛋白激酶）和 MAPK 的磷酸化表达。在患有 DCS 的对照和适应动物中均观察到即刻早期基因/转录因子早期生长反应基因 1（Egr-1）的表达，但在未患 DCS 的动物中未观察到。患有 DCS 的对照潜水动物中的 Egr-1 表达显著高于适应潜水动物中的 Egr-1 表达。患有 DCS 的对照动物中 TNF-α、IL-1β、IL-6 和 IL-10 的水平显著升高。适应-DCS 动物中 TNF-α 增加，但 IL-1β、IL-6 和 IL-10 没有变化。在适应-假潜水、适应潜水和对照潜水动物的肺中均观察到 Akt 磷酸化水平升高；只有在患有 DCS 的动物中才观察到磷酸化 ERK1/2。本研究表明，ERK1/2 的激活以及 Egr-1 和其靶细胞因子基因的上调可能在 DCS 的发生和发展中起作用。可能是患有 DCS 的动物中这些基因的下调表达与先前反复经受压缩-减压循环有关。本研究代表了理解与减压适应相关的分子机制的初步步骤。
