惰性气体神经保护作用:氙气和氩气通过不同机制预防离体大鼠海马缺氧缺血性损伤

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Noble gas neuroprotection: xenon and argon protect against hypoxic-ischaemic injury in rat hippocampus in vitro via distinct mechanisms

背景与目的

惰性气体可为缺血性和创伤性脑损伤等神经损伤提供新的治疗方法。但在同一模型中、相同条件下对全系列惰性气体进行评价少有研究。

方  法

我们用离体缺氧缺血模型来评估一系列惰性气体——氦、氖、氩、氪和氙的神经保护特性。对小鼠海马脑片进行缺氧缺糖处理,并用碘化丙啶荧光定量损伤程度。

结 果  

氙和氩都是同样有效的神经保护剂,0.5atm的氙或氩可减少96%的损伤(P<0.0001),而氦、氖和氪则没有任何保护作用。氙的神经保护作用可被升高的甘氨酸逆转,而氩气则不会。

结 论

在离体实验中,氙和氩作为神经保护剂针对缺氧缺血同样有效,两种气体均能预防损伤发生、发展。虽然氙气的神经保护作用可能是通过抑制甘氨酸位点上的N -甲基- D -天冬氨酸受体介导的,但氩气的作用机制不同。这些发现可能对其作为神经保护剂的临床应用有重要意义。

原始文献摘要

Koziakova M, Harris K, Edge CJ, et al. Noble gas neuroprotection: xenon and argon protect against hypoxic-ischaemic injury in rat hippocampus in vitro via distinct mechanisms[J]. Br J Anaesth,2019,123(5):601-609. 

Background: Noble gases may provide novel treatments for neurological injuries such as ischaemic and traumatic brain injury. Few studies have evaluated the complete series of noble gases under identical conditions in the same model.

Methods: We used an in vitro model of hypoxiaeischaemia to evaluate the neuroprotective properties of the series of noble gases, helium, neon, argon, krypton, and xenon. Organotypic hippocampal brain slices from mice were subjected to oxygen-glucose deprivation, and injury was quantifified using propidium iodide fluorescence.

Results: Both xenon and argon were equally effective neuroprotectants, with 0.5 atm of xenon or argon reducing injury by 96% (P<0.0001), whereas helium, neon, and krypton were devoid of any protective effect. Neuroprotection by xenon, but not argon, was reversed by elevated glycine.

Conclusions: Xenon and argon are equally effective as neuroprotectants against hypoxiaeischaemia in vitro, with both gases preventing injury development. Although xenon’s neuroprotective effect may be mediated by inhibition of the N-methyl-D-aspartate receptor at the glycine site, argon acts via a different mechanism. These findings may have important implications for their clinical use as neuroprotectants.

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贵州医科大学高鸿教授课题组

翻译:冯玉蓉  编辑:何幼芹  审校:王贵龙

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