孙学军：介绍治疗性气体和脑缺血转化医学

最近来自牛津大学约翰瑞德克里夫医院纳菲尔德急性中风项目Sutherland BA等写的一篇综述，目前在线发表在Curr Drug Targets.

在世界范围内，缺血性中风是发病率和死亡率都十分高。尽管用重组组织型纤维蛋白酶原激活剂（rTP, recombinant tissue plasminogen activator）可以通过溶栓恢复中断的脑血流，但有效治疗也只能局限于那些符合溶栓治疗条件的部分患者。虽然临床前证明具有神经保护作用的药物很多，但真正成功转化到临床至今没有一项。因此，大多数急性中风患者仍无法得充分有效治疗。

在急性中风领域，治疗性气体并没有受到足够重视。其实，高压氧、常压氧、氙气、氢气、氦气和氩气等治疗性气体，在缺血性中风临床前模型中全部都被证明具有神经保护作用。况且这些气体有非常明显的优点，如相对容易大量获取、价格低廉、可行性安全性强。因此，这些气体都是中风治疗理想的转化对象。

另外，具有调节细胞功能的气体信号分子，如一氧化氮、一氧化碳和硫化氢也具有引人注目的优点。虽然将呼吸这些气体和信号气体用于缺血性中风的临床治疗，仍需要进一步确认是否确实可产生理想的神经保护作用。通过分析这些治疗气体的在缺血性中风治疗中的神经保护和调节作用，作者认为，由于这些气体的天然优点，也许就是打破缺血性中风治疗转化治疗障碍的有效手段。

文献链接：
　  Inhalation Gases or Gaseous Mediators as Neuroprotectants for Cerebral Ischaemia.
　　Curr Drug Targets.2012 Nov 19. [Epub ahead of print]

　　Sutherland BA, Harrison JC, Nair SM, Sammut IA.

　　Acute Stroke Programme Nuffield, Department of Clinical Medicine, University of Oxford, Level 7, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom. brad.sutherland@ndm.ox.ac.uk.

　　Ischaemic stroke is one of the leading causes of morbidity and mortality worldwide. While recombinant tissue plasminogen activator can be administered to produce thrombolysis and restore blood flow to the ischaemic brain, therapeutic benefit is only achieved in a fraction of the subset of patients eligible for fibrinolytic intervention. Neuroprotective therapies attempting to restrict the extent of brain injury following cerebral ischaemia have not been successfully translated into the clinic despite overwhelming pre-clinical evidence of neuroprotection. Therefore, an adequate treatment for the majority of acute ischaemic stroke patients remains elusive. In the stroke literature, the use of therapeutic gases has received relatively little attention. Gases such as hyperbaric and normobaric oxygen, xenon, hydrogen, helium and argon all possess biological effects that have shown to be neuroprotective in pre-clinical models of ischaemic stroke. There are significant advantages to using gases including their relative abundance, low cost and feasibility for administration, all of which make them ideal candidates for a translational therapy for stroke. In addition, modulating cellular gaseous mediators including nitric oxide, carbon monoxide, and hydrogen sulphide may be an attractive option for ischaemic stroke therapy. Inhalation of these gaseous mediators can also produce neuroprotection, but this strategy remains to be confirmed as a viable therapy for ischaemic stroke. This review highlights the neuroprotective potential of therapeutic gas therapy and modulation of gaseous mediators for ischaemic stroke. The therapeutic advantages of gaseous therapy offer new promising directions in breaking the translational barrier for ischaemic stroke.

来源：光明网