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在减压条件下家兔血脑屏障对四环素的通透性增加。

Increased blood-brain barrier permeability to tetracycline in rabbits under dysbaric conditions.

作者信息

Chryassanthou C, Graber B, Mendelson S, Goldstein G

出版信息

Undersea Biomed Res. 1979 Dec;6(4):319-28.

PMID:538860
Abstract

Alteration of the blood-brain barrier (BBB) by dysbaric exposure may have relevance in several areas of hyperbaric medicine. Drugs administered to persons exposed to dysbaric conditions, e.g., divers, compressed air workers, may penetrate the brain in amounts that could produce toxic or undesirable effects. Modification of the BBB may also have pathogenetic implications in decompression sickness. Furthermore, increased BBB permeability to certain potentially useful antitumor agents, antibiotics, and other compounds under dysbaric conditions may provide the basis for a new therapeutic approach. This report concerns the influence of dysbaric exposure on BBB permeability to an antibiotic. Tetracycline (5-40 mg/kg) was intravenously injected in 22 experimental rabbits (subjected to air compression-decompression) and 17 controls (kept at ambient pressure). Fluorescence microscopy and spectrometry revealed significantly greater tetracycline concentrations in 72.7% of the experimental brains. With the 5 mg/kg dose, the mean tetracycline concentrations was 0.17 micrograms/g in control brains and 0.33 micrograms/g in experimentals. These results indicate that dysbaric exposure increases BBB permeability to tetracycline. It appears that BBB alteration is related to intravascular gas bubbles but is independent of the development of decompression sickness. The conclusions of this investigation are pertinent to brain pharmacotherapy and may provide some new insight into the mechanism of decompression sickness. They also point to potential risks connected with drug administration under dysbaric conditions that can alter BBB permeability.

摘要

高压暴露对血脑屏障(BBB)的改变可能在高压医学的多个领域具有相关性。给予处于高压环境中的人员(如潜水员、压缩空气作业工人)的药物,可能会以产生毒性或不良影响的量穿透大脑。血脑屏障的改变在减压病中也可能具有发病机制方面的意义。此外,在高压条件下血脑屏障对某些潜在有用的抗肿瘤药物、抗生素和其他化合物的通透性增加,可能为一种新的治疗方法提供基础。本报告关注高压暴露对血脑屏障对抗生素通透性的影响。将四环素(5 - 40毫克/千克)静脉注射到22只实验兔(接受空气压缩 - 减压)和17只对照兔(保持在常压下)体内。荧光显微镜检查和光谱分析显示,72.7%的实验兔大脑中的四环素浓度显著更高。以5毫克/千克的剂量为例,对照兔大脑中四环素的平均浓度为0.17微克/克,实验兔为0.33微克/克。这些结果表明,高压暴露会增加血脑屏障对四环素的通透性。看来血脑屏障的改变与血管内气泡有关,但与减压病的发生无关。本研究的结论与脑药物治疗相关,可能为减压病的机制提供一些新的见解。它们还指出了在能改变血脑屏障通透性的高压条件下给药所存在的潜在风险。

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