氧气是需氧生物不可缺少的物质，但氧气本身也有毒性，最典型的就是呼吸纯氧可以引起肺损伤。这种肺损伤是对肺功能障碍患者急救吸氧时遇到的严重问题，不吸氧会缺氧，吸氧会导致肺功能进一步恶化，一旦患者遇到这种进退不得的局面，往往无法挽救生命。氢气作为一种治疗性气体，最近发现呼吸氢气对移植肺损伤有很好的保护作用，这种作用和血红素加氧酶heme oxygenase (HO)-1被诱导有关系，为证明呼吸氢气是否可以保护高氧诱导的肺损伤以及机制，本研究将大鼠随机分成4组，分别将不同混合气体处理动物60小时，98%氧气2%氮，98%氧气2%氢，98%空气2%氮，98%空气2%氢。然后用血液气体分析检测肺功能，肺损伤程度和HO-1表达情况。同时检测Nrf 2，以及氢气对Nrf 2基因缺乏动物肺损伤的作用。结果发现，氢气可以显著提高血氧饱和度，减少炎症反应，诱导HO-1表达，但在Nrf 2基因缺乏动物，氢气无法产生保护作用，也无法诱导HO-1表达。这些结果说明，氢气可以对抗高氧引起的肺损伤，这种保护作用和Nrf 2以来的抗氧化基因表达有关。实验结束后，没有经过治疗的动物64小时内几乎全部死亡，而治疗组动物平均存活时间72小时。这一研究提示氢气可以作为治疗高氧肺损伤，对临床上挽救这些患者的生命提供一种潜在手段，这种保护作用的分子机制和氢气诱导内源性抗氧化系统有关。

这是第一次比较明确的分子机制研究，说明氢气的许多抗氧化作用并不是自己的抗氧化作用，而是通过提高细胞自身的抗氧化能力实现的。将来的研究应该分析氢气为什么具有诱导NRF2的作用。是直接调节，还是通过其他分子间接发挥作用。毕竟现在找到一个比较重要的分子靶点。本研究值得关注。

Am J Physiol Lung Cell Mol Physiol. 2013 Mar 8. [Epub ahead of print]

Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo.

Kawamura T, Wakabayashi N, Shigemura N, Huang CS, Masutani K, Tanaka Y, Noda K, Peng X, Takahashi T, Billiar TR, Okumura M, Toyoda Y, Kensler TW, Nakao A.

1University of Pittsburgh Medical Center.

Hyperoxic lung injury is a major concern in critically ill patients who receive high concentrations of oxygen to treat lung diseases. Successful abrogation of hyperoxic lung injury would have a huge impact on respiratory and critical care medicine.

Hydrogen can be administered as a therapeutic medical gas. We recently demonstrated that inhaled hydrogen reduced transplant-induced lung injury and induced heme oxygenase (HO)-1. To determine whether hydrogen could reduce hyperoxic lung injury and investigate the underlying mechanisms, we randomly assigned rats to 4 experimental groups and administered the following gas mixtures for 60 hours: 98% oxygen (hyperoxia), 2% nitrogen; 98% oxygen (hyperoxia), 2% hydrogen; 98% balanced air (normoxia), 2% nitrogen; and 98% balanced air (normoxia), 2% hydrogen. We examined lung function by blood gas analysis, extent of lung injury, and expression of HO-1. We also investigated the

role of NF-E2-related factor (Nrf) 2, which regulates HO-1 expression, by examining the expression of Nrf2-dependent genes and the ability of hydrogen to reduce hyperoxic lung injury in Nrf2-deficient mice.

Hydrogen treatment during exposure to hyperoxia significantly improved blood oxygenation, reduced inflammatory events, and induced HO-1 expression. Hydrogen did not mitigate hyperoxic lung injury or induce HO-1 in Nrf2-deficient mice. These findings indicate that hydrogen gas can ameliorate hyperoxic lung injury through induction of Nrf2-dependent genes, such as HO-1. The findings suggest a potentially novel and applicable solution to hyperoxic lung injury, and provide new insight into the molecular mechanisms and actions of hydrogen.

PMID: 23475767  [PubMed - as supplied by publisher]