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反复进行高压氧暴露通过上调内皮型一氧化氮合酶(eNOS)和神经元型一氧化氮合酶(nNOS)来增强对惊厥的敏感性。

Repetitive hyperbaric oxygen exposures enhance sensitivity to convulsion by upregulation of eNOS and nNOS.

作者信息

Liu Wenwu, Li Jiasi, Sun Xuejun, Liu Kan, Zhang John H, Xu Weigang, Tao Hengyi

机构信息

Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, and Department of Neurology, Changhai Hospital, Shanghai, 200433, PR China.

出版信息

Brain Res. 2008 Mar 27;1201:128-34. doi: 10.1016/j.brainres.2008.01.068. Epub 2008 Feb 5.

Abstract

BACKGROUND

Repetitive hyperbaric oxygen (HBO) exposures as preconditioning methods produce ischemic tolerance, but may increase the risk of convulsions in patients. The purpose of this study was to investigate the mechanisms in increased sensitivity to convulsions and the role of nitric oxide (NO) and its synthases after repetitive HBO exposures.

METHODS

Mice were randomly assigned into three groups: HBO group, hyperbaric air (HBA) group and normobaric air (NBA) group. Mice in HBO or HBA group were exposed to hyperbaric oxygen or hyperbaric air respectively for 60 min twice daily for 3 consecutive days (2.5 atmosphere absolute [ATA]). 24 h after the last exposure, mice were exposed to HBO (100% O2, 6 ATA). The latency of convulsions was recorded. In addition, the levels of NO, NADPH-diaphorase, mRNA and protein expressions of NOS isoforms in hypothalamus and hippocampus were determined.

RESULTS

Latency to seizures was significantly shortened in mice after six HBO pre-exposures. The level of NO in hypothalamus in HBO group was increased. The number of NADPH-d positive cells and the levels of protein and mRNA of eNOS and nNOS in hypothalamus and hippocampus were increased.

CONCLUSION

After repeated HBO exposures, elevated NO may enhance the sensitivity to convulsions and this may lead to seizures during the subsequent oxygen exposures. Prevention of seizures is needed when HBO is used as preconditioning method.

摘要

背景

重复进行高压氧(HBO)暴露作为预处理方法可产生缺血耐受性,但可能会增加患者惊厥的风险。本研究的目的是探讨重复HBO暴露后惊厥敏感性增加的机制以及一氧化氮(NO)及其合酶的作用。

方法

将小鼠随机分为三组:HBO组、高压空气(HBA)组和常压空气(NBA)组。HBO组或HBA组的小鼠分别每天两次暴露于高压氧或高压空气中60分钟,连续3天(绝对气压2.5个大气压[ATA])。最后一次暴露后24小时,将小鼠暴露于HBO(100% O₂,6 ATA)。记录惊厥潜伏期。此外,测定下丘脑和海马中NO的水平、NADPH-黄递酶、NOS亚型的mRNA和蛋白表达。

结果

经过六次HBO预处理后,小鼠惊厥潜伏期显著缩短。HBO组下丘脑NO水平升高。下丘脑和海马中NADPH-d阳性细胞数量以及eNOS和nNOS的蛋白和mRNA水平升高。

结论

重复HBO暴露后,升高的NO可能会增强惊厥敏感性,这可能导致随后吸氧期间发生惊厥。当使用HBO作为预处理方法时,需要预防惊厥。

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