Thom S R
University of Pennsylvania, Institute for Environmental Medicine, Philadelphia 19104-6068.
Toxicol Appl Pharmacol. 1993 Dec;123(2):248-56. doi: 10.1006/taap.1993.1243.
Exposure to hyperbaric oxygen [3 atmospheres absolute (ATA) for 45 min] inhibited carbon monoxide (CO)-mediated lipid peroxidation in the brains of rats by preventing the conversion of xanthine dehydrogenase to oxidase, a conversion process known to be due to the action of leukocytes. The effect was the same whether treatment was given 24 hr before or up to 45 min after poisoning. Hyperbaric oxygen did not inhibit the initial interaction of leukocytes with brain microvasculature, based on measurements of myeloperoxidase (MPO) in microvessel segments, but persistent adherence, which is due to B2 integrins, did not occur. Exposing rats to 3 ATA pressure (0.21 ATA O2) after CO poisoning had no significant effects. A progressive reduction in brain microvessel MPO titers occurred with exposure to O2 at 1, 2, or 3 ATA after CO poisoning, but 1 ATA O2 treatment did not significantly inhibit xanthine oxidase formation or lipid peroxidation. In vitro studies with polymorphonuclear leukocytes (PMN) from rats exposed to hyperbaric oxygen corroborated the absence of PMN B2 integrin function, but when these cells were stimulated they exhibited normal B2 integrin expression on their surface and also normal elastase release and superoxide radical production. Adherence functions of PMN that do not require B2 integrins appeared to remain intact after exposure to hyperbaric oxygen, as peritoneal neutrophilia in response to a glycogen challenge was not inhibited. B2 integrin function could be restored by incubating cells with 8 bromo cGMP, and incubation with phorbol ester stimulated the adherence function of both control and hyperbaric oxygen-exposed PMN. These results provide a clear mechanism for the inhibition of CO-mediated brain lipid peroxidation by hyperbaric oxygen and indicate that hyperoxia causes a discrete disturbance of PMN adherence function.
暴露于高压氧（3个绝对大气压（ATA），持续45分钟）可通过阻止黄嘌呤脱氢酶向氧化酶的转化来抑制大鼠脑中一氧化碳（CO）介导的脂质过氧化，已知这种转化过程是由白细胞的作用引起的。无论在中毒前24小时还是中毒后45分钟内进行治疗，效果都是相同的。基于对微血管段中髓过氧化物酶（MPO）的测量，高压氧并未抑制白细胞与脑微血管的初始相互作用，但由于B2整合素导致的持续黏附并未发生。CO中毒后将大鼠暴露于3 ATA压力（0.21 ATA O₂）没有显著影响。CO中毒后，暴露于1、2或3 ATA的O₂会使脑微血管MPO滴度逐渐降低，但1 ATA O₂治疗并未显著抑制黄嘌呤氧化酶的形成或脂质过氧化。对暴露于高压氧的大鼠多形核白细胞（PMN）进行的体外研究证实了PMN B2整合素功能的缺失，但当这些细胞受到刺激时，它们在表面表现出正常的B2整合素表达，并且弹性蛋白酶释放和超氧自由基产生也正常。暴露于高压氧后，不需要B2整合素的PMN黏附功能似乎保持完整，因为对糖原刺激的腹膜嗜中性粒细胞增多并未受到抑制。通过用8-溴-cGMP孵育细胞可以恢复B2整合素功能，用佛波酯孵育可刺激对照和暴露于高压氧的PMN的黏附功能。这些结果为高压氧抑制CO介导的脑脂质过氧化提供了明确的机制，并表明高氧会导致PMN黏附功能的离散性紊乱。
