Hong Yunchuan, Sun L I, Sun Ruiqiang, Chen Hongguang, Yu Yonghao, Xie Keliang
Department of Respiratory Medicine, General Hospital of Tianjin Medical University, Tianjin 300052, P.R. China.
Department of Anesthesiology, General Hospital of Beijing Military Command, Beijing 100700, P.R. China.
Exp Ther Med. 2016 Jun;11(6):2590-2596. doi: 10.3892/etm.2016.3231. Epub 2016 Apr 6.
Multiple organ dysfunction syndrome (MODS) is a leading cause of mortality in critically ill patients. Hyperoxia treatment may be beneficial to critically ill patients. However, the clinical use of hyperoxia is hindered as it may exacerbate organ injury by increasing reactive oxygen species (ROS). Hydrogen gas (H) exerts a therapeutic antioxidative effect by selectively reducing ROS. Combination therapy of H and hyperoxia has previously been shown to significantly improve survival rate and organ damage extent in mice with polymicrobial sepsis. The aim of the present study was to investigate whether combination therapy with H and hyperoxia could improve survival rate and organ damage in a zymosan (ZY)-induced generalized inflammation model. The results showed that the inhalation of H (2%) or hyperoxia (98%) alone improved the 14-day survival rate of ZY-challenged mice from 20 to 70 or 60%, respectively. However, combination therapy with H and hyperoxia could increase the 14-day survival rate of ZY-challenged mice to 100%. Furthermore, ZY-challenged mice showed significant multiple organ damage characterized by increased serum levels of aspartate transaminase, alanine transaminase, blood urea nitrogen and creatinine, as well as lung, liver and kidney histopathological scores at 24 h after ZY injection. These symptoms where attenuated by H or hyperoxia alone; however, combination therapy with H and hyperoxia had a more marked beneficial effect against lung, liver and kidney damage in ZY-challenged mice. In addition, the beneficial effects of this combination therapy on ZY-induced organ damage were associated with decreased serum levels of the oxidative product 8-iso-prostaglandin F2α, increased activity of superoxide dismutase and reduced levels of the proinflammatory cytokines high-mobility group box 1 and tumor necrosis factor-α. In conclusion, combination therapy with H and hyperoxia provides enhanced therapeutic efficacy against multiple organ damage in a ZY-induced generalized inflammation model, suggesting the potential applicability of H and hyperoxia in the therapy of conditions associated with inflammation-related MODS.
多器官功能障碍综合征（MODS）是危重症患者死亡的主要原因。高氧治疗可能对危重症患者有益。然而，高氧的临床应用受到阻碍，因为它可能通过增加活性氧（ROS）而加重器官损伤。氢气（H₂）通过选择性地减少ROS发挥治疗性抗氧化作用。先前已证明，H₂与高氧联合治疗可显著提高多重微生物败血症小鼠的存活率并减轻器官损伤程度。本研究的目的是探讨H₂与高氧联合治疗是否能改善酵母聚糖（ZY）诱导的全身炎症模型中的存活率和器官损伤。结果表明，单独吸入H₂（2%）或高氧（98%）可将ZY攻击小鼠的14天存活率分别从20%提高到70%或60%。然而，H₂与高氧联合治疗可将ZY攻击小鼠的14天存活率提高到100%。此外，ZY攻击小鼠在注射ZY后24小时表现出明显的多器官损伤，其特征为血清天冬氨酸转氨酶、丙氨酸转氨酶、血尿素氮和肌酐水平升高，以及肺、肝和肾组织病理学评分升高。这些症状单独用H₂或高氧可减轻；然而，H₂与高氧联合治疗对ZY攻击小鼠的肺、肝和肾损伤具有更显著的有益作用。此外，这种联合治疗对ZY诱导的器官损伤的有益作用与氧化产物8-异前列腺素F2α的血清水平降低、超氧化物歧化酶活性增加以及促炎细胞因子高迁移率族蛋白B1和肿瘤坏死因子-α水平降低有关。总之，H₂与高氧联合治疗在ZY诱导的全身炎症模型中对多器官损伤具有增强的治疗效果，提示H₂和高氧在与炎症相关的MODS相关疾病治疗中的潜在适用性。
