这里介绍一篇来自《休克》的读者来信，来信中针对氢气的生物学效应机制提出一种理论，认为氢气可以通过影响微循环发挥生物学效应，如果说从微循环角度探讨氢气对一些疾病的治疗作用值得考虑，但把这种寻找证据的说法上升到理论的说法并不妥当。

2007年Nature Medicine上一篇关于氢气治疗疾病的研究启动了氢气生物学效应的研究。Ohsawa等同时提供了研究模式，吸引了大量学者的跟踪研究。他们的研究中发现氢气具有保护脑缺血再灌注损伤，可以通过选择性清除毒性自由基，特别是羟自由基和亚硝酸阴离子，这些毒性自由基是活性氧中作用最为强烈。随后的研究证明氢气不仅是抗氧化作用，还具有抗炎症、凋亡等效应，在各类器官如肝、肺、心、肾、小肠等损伤和疾病中均可发挥保护作用。使用氢气至少可以通过呼吸、饮用和注射氢气溶液的手段，谢等发现呼吸氢气可以通过降低HMGB1，减少氧化损伤对脓毒症具有治疗作用。Nagatani最近发现氢气可以通过影响细胞自噬保护全脑缺血损伤，提高动物生存率。

关于氢气医学的研究，现在显然遇到瓶颈。尽管越来越多的疾病被证明可以用氢气治疗，但没有一项研究清楚这种效果的本质。经典的解释也遇到质疑和挑战。因此非常需要新的理论来解释。本文作者曾经提出一种新的概念，认为氢气和一氧化氮、一氧化碳和硫化氢一样，也属于一种气体信号分子。

显然这也不能完全解释这种小剂量气体分子的效应。这里作者对这一概念重新考虑，无论是呼吸，还是注射等给氢气手段，氢气必须首先进入血管，这意味着氢气可以直接进入循环系统。但是没有人注意到微循环和氢气分子是否存在关系（这里逻辑上不通，可进入循环或微循环不一定就会有作用）。微循环是一种复杂的系统，对多种生理或病理生理过程具有重要作用。其中存在大量信号分子或蛋白之间的相互作用。那么，为什么不可以预测氢气分子对微循环可以产生影响。如对一些相关生物分子如抗氧化酶、自由基和炎症分子（这些已经都非常明确）。如果这个理论被证明存在，将是对经典理论的很好补充。   许多研究已经证明氢气是一种新的治疗手段，对机体没有任何伤害性作用。我们应该努力将这一手段从基础研究推向临床。另一方面，探索分子机制也十分必要。我们相信氢气对微循环效应的研究将可以打破僵局，促进氢气生物学效应机制的深入开展。

个人看法，氢气的生物学效应比较明确，对各类疾病过程中的氧化损伤、炎症和细胞坏死等具有很好的治疗效果，微循环是许多器官组织中具有重要功能的单位，氢气在器官水平和细胞水平上的作用自然可以推广到微循环水平上。因此，从这个角度考虑问题并没有突破过去的研究思路，只是在不同侧面对同一个问题的描述。因此尚不足以构成理论或假说。

Effect of Hydrogen Gas on the Survival Rate of Mice Following Global Cerebral Ischemia (Shock 37(6), 645–652, 2012)

Zhang, JingYao; Liu, Chang; Tai, MingHui; Qu, Kai

Author Information

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, China

Back to Top  

Effect of Hydrogen Gas on the Survival Rate of Mice Following Global Cerebral Ischemia. Shock 37(6):645–652, 2012  

To the Editor

In 2007, an article about hydrogen acting as a miracle therapy was published in Nature, it symbolized that a new field of medicine was created. At the same time, Ohsawa et al, (1) provided a template of such a study, which attracted hundreds of followers. In the research, they discovered that hydrogen gas has the ability to protect the brain against ischemia-reperfusion injury, through selectively eliminating the toxic oxygen radicals, especially the hydroxyl radicals and peroxynitrite, which are two of the strongest of the oxidant species. The follow-up studies proved that hydrogen really has the ability of antioxidant, anti-inflammatory, antiapoptotic, and other protective effects in various organ systems, including the lung, liver, heart, kidneys, intestines, and brain. And the way of delivery developed from inhalation to drinking and at last the injection of the hydrogen-rich saline (2). Two of such studies were published in Shock. Xie et al. (3) found that inhalation of hydrogen had a good effect on the murine polymicrobial sepsis via reducing oxidative stress and HMGB1 release. Recently, Nagatani et al. (4) first reported that hydrogen gas could increase the survival rate of mice following global cerebral ischemia by impacting the autophagy. It proved again the magic effect of the hydrogen therapy.

When we reviewed the articles about hydrogen medicine, we had to admit that this field had met the bottleneck. Although more and more diseases were proven effective by using hydrogen therapy, no one could reach the essence of such miraculous phenomenon. Now the traditional mechanism is questioned and challenged; it is badly in need of the new blood, which can enrich the theory systems. In my previous article, I submitted a concept that the hydrogen acted as the fourth gaseous signaling molecule after nitric oxide, carbon monoxide, and hydrogen sulfide (2).

Obviously, it could not explain completely the huge effect under such small doses. So when we rethought the process of the hydrogen admitted into the organisms, whatever inhalation or injection into the abdomen, the hydrogen first contacted with the vessels, meaning the hydrogen molecule can penetrate into the microcirculation straightforward. Unfortunately, no one paid attention to the relationship between the microcirculation and the hydrogen molecule. The microcirculation is a complex system that has a lot of important effects on the whole physiology and pathology processes (5). One of these is the amplification of some signal molecules or some proteins—the cascade reaction (6). So, why can we not predict that the hydrogen molecule has a positive effect on the microcirculation, and through the amplification effect, the organism can produce a remarkable variation of the biochemical indicator, including the increase of the antioxidant enzyme and elimination of the reactive oxygen species or some inflammatory factors? If this theory can prove that it really existed, it will be a perfect complement to the traditional theory.

Thus, many researches have demonstrated that hydrogen is a new miracle medical therapy with almost no harm to the organism. We should try our best to make it bench-to-bed. On the other hand, the exploration of the mechanism is also an eager necessity. We believe the effect of hydrogen on the microcirculation can be a breakthrough in this field in the future.

JingYao Zhang

Chang Liu

MingHui Tai

Kai Qu

Department of Hepatobiliary Surgery

The First Affiliated Hospital of

Xi’an Jiaotong University

Xi’an, China

Back to Top  

REFERENCES  

1. Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, Katsura K, Katayama Y, Asoh S, Ohta S: Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med 13: 688–694, 2007. Bibliographic Links Library Holdings [Context Link]

2. Zhang JY, Liu C, Zhou L, Qu K, Wang R, Tai MH, Lei Lei JC, Wu QF, Wang ZX: A review of hydrogen as a new medical therapy. Hepatogastroenterology 2012 Jun;59(116): 1026–32. [Context Link]

3. Xie K, Yu Y, Pei Y, Hou L, Chen S, Xiong L, Wang G.: Protective effects of hydrogen gas on murine polymicrobial sepsis via reducing oxidative stress and HMGB1 release. Shock 34 (1): 90–97, 2010. [Context Link]

4. Nagatani K, Wada K, Takeuchi S, Kobayashi H, Uozumi Y, Otani N, Fujita M, Tachibana S, Nawashiro H: Effect of hydrogen gas on the survival rate of mice following global cerebral ischemia. Shock 37 (6): 645–652, 2012. Ovid Full Text Bibliographic Links Library Holdings [Context Link]

5. Lafont C, Desarménien MG, Cassou M, Molino F, Lecoq J, Hodson D, Lacampagne A, Mennessier G, El Yandouzi T, Carmignac D, et al.: Cellular in vivo imaging reveals coordinated regulation of pituitary microcirculation and GH cell network function. Proc Natl Acad Sci U S A 107 (9): 4465–4470, 2010. [Context Link]

6. Dahl KN, Kalinowski A, Pekkan K. Mechanobiology and the microcirculation: cellular, nuclear and fluid mechanics. Microcirculation 17 (3): 179–191, 2010. Bibliographic Links Library Holdings [Context Link]