氢气在多种中枢神经损伤模型中被证明有很好的神经保护作用，其作用机制一般都归因于氢气的抗氧化作用。来自美国Loma Linda大学Manaenko等关于呼吸氢气对小鼠脑出血的治疗作用和氢气可以阻断出血后脑组织内肥大细胞激活有关的文章。最近发表在国际知名杂志Crit Care Med上。

肥大细胞mast cell是和血液的嗜碱粒细胞同样，具有强嗜碱性颗粒的组织细胞。存在于血液中的这类颗粒，含有肝素、组织胺、5-羟色胺，由细胞崩解释放出颗粒以及颗粒中的物质，可在组织内引起速发型过敏反应（炎症）。由于在肥大细胞上结合的IgE抗体和抗原的接触，使细胞多陷于崩坏。脑缺血和脑出血也存在炎症反应，也会在早期（６小时）出现肥大细胞的浸润和激活。在脑缺血和脑出血的炎症反应中发挥重要作用。

由于曾经有学者报道，氢气可以通过阻断肥大细胞激活对皮肤过敏具有治疗作用（2009 BBRC），那么考虑到氢气对脑出血具有治疗作用，是否其治疗作用也和阻断肥大细胞激活有关。这一研究正是沿着这一思路开展。

首先用胶原酶脑内注射诱导出脑出血模型，呼吸氢气治疗，采用出血后２４小时７２小时血脑屏障、神经功能评价作为整体效果的分析，用western blot和免疫组织化学方法确定肥大细胞激活清楚（出血后６小时，千万不要检测２４小时和７２小时的情况）。治疗效果最后采用自体血注射脑出血模型确认（胶原酶模型毕竟和真实的出血不同，采用多个模型相互验证可以提高结果的可信度）。研究结果发现，模型组动物代表肥大细胞激活的Lyn激酶磷酸化水平提高，胰酶释放增加，肥大细胞脱颗粒情况增加。而氢气治疗组在脑屏障和神经功能改善的情况下，上述改变都受到抑制，说明氢气治疗脑出血有效，而且和阻断肥大细胞激活有关。

关于氢气生物学研究目前似乎走到一个瓶颈，大家无法找到理想的研究模式，其原因很多，其中一种原因是受到研究者思路的限制，大家不愿意或不敢提出自己的想法，只按照别人的研究思路，这非常不利于问题的解决。从总体上考虑，氢气的作用很明确，机制不清楚，那么怎么探讨，从什么角度探讨都不应该限制，可能目前最好的方法是不考虑作用的重要性，只考虑是否参与，最后再慢慢比较和确认最合理的解释和途径。

Crit Care Med. 2013 Feb 5. [Epub ahead of print]

Hydrogen Inhalation Ameliorated Mast Cell-Mediated Brain Injury After

Intracerebral Hemorrhage in Mice.

Manaenko A, Lekic T, Ma Q, Zhang JH, Tang J.

Department of Physiology and Pharmacology, Loma Linda University Medical Center,

Loma Linda, CA. This work is attributed to the Department of Physiology and

Pharmacology, Loma Linda University, Loma Linda, CA.

OBJECTIVE:: Hydrogen inhalation was neuroprotective in several brain injury

models. Its mechanisms are believed to be related to antioxidative stress. We

investigated the potential neurovascular protective effect of hydrogen inhalation

especially effect on mast cell activation in a mouse model of intracerebral

hemorrhage. DESIGN:: Controlled in vivo laboratory study. SETTING:: Animal

research laboratory. SUBJECTS:: 171, 8-wk-old male CD-1 mice were used.

INTERVENTIONS:: Collagenase-induced intracerebral hemorrhage model in 8-wk-old

male CD-1 mice was used. Hydrogen was administrated via spontaneous inhalation.

The blood-brain barrier permeability and neurological deficits were investigated

at 24 and 72 hrs after intracerebral hemorrhage. Mast cell activation was

evaluated by Western blot and immuno-staining. The effects of hydrogen inhalation

on mast cell activation were confirmed in an autologous blood injection model

intracerebral hemorrhage. MEASUREMENT AND MAIN RESULTS:: At 24 and 72 hrs post

intracerebral hemorrhage, animals showed blood-brain barrier disruption, brain

edema, and neurological deficits, accompanied with phosphorylation of Lyn kinase

and release of tryptase, indicating mast cell activation. Hydrogen treatment

diminished phosphorylation of Lyn kinase and release of tryptase, decreased

accumulation and degranulation of mast cells, attenuated blood-brain barrier

disruption, and improved neurobehavioral function. CONCLUSION:: Activation of

mast cells following intracerebral hemorrhage contributed to increase of

blood-brain barrier permeability and brain edema. Hydrogen inhalation preserved

blood-brain barrier disruption by prevention of mast cell activation after

intracerebral hemorrhage.

PMID: 23388512  [PubMed - as supplied by publisher]