慢性氧中毒即使一种研究氧气慢性毒性的模型，也是一种比较理想的研究慢性肺损伤的模型。慢性氧中毒模型是一种非常好的动物模型，因为可以根据需要调整氧气的浓度、暴露时间和暴露压力，能制备出不同程度的肺损伤模型。
慢性氧中毒是患者呼吸高分压氧（60%）时发生的一种疾病。当患者因肺功能障碍需要通过呼吸高浓度氧来维持血氧饱和度时，就会出现非常令人尴尬的局面：如果不提高呼吸气体的氧浓度，患者会发生缺氧，如果提高呼吸气体的氧浓度，氧气本身会增加肺损伤。一旦患者到了这个处境，也意味着到了绝境。这种情况在医院的ICU是经常遇到的。
慢性氧中毒的主要原因是呼吸高分压氧增加了肺组织内的活性氧，后者导致肺组织发生氧化损伤，最有效的方法是降低氧分压。当患者需要呼吸氧气的时候，必须采取间隔呼吸氧气的方法，这样才可以有效降低氧气的毒性（高压氧治疗采用间歇呼吸氧气也有这个考虑）。慢性氧中毒早期改变类似于支气管肺炎的改变，如果不能及时降低氧分压，患者将会出现炎症加重，并最终导致肺纤维化，这个过程非常类似于病毒性肺炎（非典型肺炎），在非典期间，我曾经建议采用这个模型来研究药物，特别是非抗病毒性药物。
氢气抗氧化的发现后，结合我们过去有许多研究慢性氧中毒的经验，我们早就开始了用氢气治疗这个疾病的研究（同时开展对急性氧中毒的研究，发现没有治疗效果）。数月前，我们已经用2个大气压短时间（6小时）暴露的慢性氧中毒模型证明了氢气对慢性氧中毒的效果，文章发表在Undersea and Hyperbaic medicine上。由于考虑到慢性氧中毒更多发生在常压呼吸氧气的情况，我们现在又采用常压吸氧48小时的模型重复了该研究，并通过炎症因子测定，抗氧化酶测定和细胞凋亡检测进行相对深入的研究。这个研究论文被J Surgical Res接受(全文pdf）。
在投稿过程中，有一个小插曲，我们与美国匹兹保大学Nakao教授就这个课题多次交换过意见，他们也进行了相关研究，我们开始希望他做共同作者，他没有接受我们的建议。而且由于我们的文章写的比较早，他们提出让我们推迟投稿3个月，等他们的文章出来大家一起投稿。我虽然觉得他有一些过分，因为这个研究是我们独立完成的。但考虑到大家将来的合作，也不太懂这方面的情况到底如何处理，我们最后还是把这个文章就延迟了几个月才投稿。
该文章第一作者我们博士研究生，这是他以第一作者发表的第4篇SCI论文，今天上午正好去美国美国匹兹保大学器官移植中心Nakao教授从事合作研究。写下此文以做留念，并祝愿他在美国的工作生活顺利，在Nakao教授的指导下，做出更加精彩的研究。
Hydrogen-Rich Saline Provides Protection Against Hyperoxic Lung Injury
Qiang Sun.*, Jianmei Cai†, Shulin Liu*, Yun Liu*, Weigang Xu*, Hengyi Tao*, , , and Xuejun Sun Ph.D., M.D.*,
† Department of Neurology, Changhai Hospital, 174 Changhai Road, Shanghai, PR China
* Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, PR China
Received 21 August 2010.
Available online 15 October 2010.
Background
Hydrogenhas been proven to be a novel antioxidant through its selectively reducing of the hydroxyl radical. In this study, we investigated the effects of hydrogen-rich salineon the prevention of acute lung injuryinduced by hyperoxia (HALI) in rats.
Materials and Methods
Physiologic saline, hydrogen-rich saline,or nitrogen-rich salinewas administered through intraperitoneal (i.p.) injection during exposure to hyperoxia (10 mL/Kg), respectively.
Results
Severity of HALI was assessed by the volume of pleural effusion, wet-to-dry weight ratio (W/D), and histologic analysis. Apoptosis in lungcells was determined with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive staining. The content of pro-inflammatory cytokine interleukin IL-1b and TNF-a in the lungtissues were detected by enzyme-linked immunosorbent assay (ELISA). Hydrogen-rich salinetreatment provides protection againstHALI by inhibiting lipid, DNA oxidation, and tissue edema. Moreover, hydrogen-rich salinetreatment could inhibit apoptosis and inflammation while no significant reduction was observed in nitrogen-rich salinetreated animals.
Conclusion
The results of this study demonstrate that hydrogen-rich salineameliorated hyperoxia-induced acute lung injuryby reducing oxidative stress and inflammatory cascades in lungtissue.
Key Words: hydrogen; acute lung injury; oxidative stress; inflammation; apoptosis
Hyperoxicacute lung injury(HALI), caused by prolonged supplement of very high concentrations of oxygen (fractional concentrations of oxygen > 50%), is a clinical syndrome characterized by endothelial and epithelial injuryand enhanced alveolar capillary protein leak [1], [2], [3], [4], [5] and [6]. It is generally accepted that increased generation of reactive oxygen species (ROS) plays an important role in lung injuryduring exposure to hyperoxia [7], [8] and [9]. To evaluate antioxidant defenses, a principal focus of prior studies has been on antioxidant enzymes such as superoxide dismutase (SOD) [10] and [11], GSH peroxidase (GPx) [12] and [13], and peroxiredoxin 6 [14] and [15]utilizing both overexpression and suppression of activity. In addition, subsequent reports indicated that IL-1, tumor necrosis factor (TNF)-a and IL-6 induce tolerance [1] and [16]. As yet, there are no specific treatments for HALI available and new effective treatment are needed for clinical settings.
Hydrogenis a gaseous molecule without known toxicity, which could react with hydroxyl radical, has been considered as a novel antioxidant [17]. Both in vivo and in vitro studies support the protective effect of hydrogenon ischemia-reperfusion injuriescaused by oxidative stress in brain [18], liver [19], heart [20], [21] and [22], and intestine [23], as well as anti-inflammatory effect on acute pancreatitis [24], colon inflammation [25], liver inflammation [26].
Our previous study has demonstrated that hydrogen-rich salinecould reduce lung injuryinduced by intestinal ischemia/reperfusion in rats [27]. This raises the possibility that the hydrogen-rich salinemight lead to protection againstHALI. Therefore, the present study investigated the possible therapeutic effects of hydrogen-rich saline on lung injuryinduced by hyperoxia in rats.（科学网孙学军的博客）
