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氢氧混合气吸入可治疗脓毒症
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Combination therapy with molecular hydrogen and hyperoxia in a murine model of p.pdf
脓毒症是重症监护病房内最常见的死亡原因，有研究发现，高浓度氧对脓毒症有一定价值。然而，由于高浓度氧通过提高自由基水平对肺组织可能造成伤害，这限制了高浓度氧的临床应用。最近有人发现，低浓度氢气呼吸可以产生良好的对抗自由基，发挥抗氧化作用，减少氧化应激，预防脓毒症。因此，如果联合氢气和氧气治疗脓毒症，应该可以产生优势互补的效应。最近发表在《休克》杂志上的一项研究就是利用这一研究思路，观察了氢气氧气联合呼吸治疗脓毒症的效果。研究来自天津医科大学谢克亮研究小组。
研究发现，分别呼吸H2（2％）或高氧（98％），结果发现可以显著提高中型脓毒症动物14天的生存率（从40％到80％或70％），如果联合两种方法，则可以是中型脓毒症动物生存率提高到100%。对严重的脓毒症，14天的生存率从0%提高到70%。其他相关指标，例如髓过氧化物酶活性、肺湿/干重量比、支气管肺泡灌洗液蛋白质水平、血清生化指标（谷丙转氨酶、谷草转氨酶浓度、肌酐和血中尿素氮）、器官组织病理学评分（肺，肝，肾）、PaO2/FiO2比值等各项指标均符合治疗有效和联合效果增强的推测。此外，联合两种方法显著减少血清和组织中氧化产物（8 - 异前列腺素F2），增加抗氧化酶活性（超氧化物歧化酶（SOD）和过氧化氢酶）和抗炎细胞因子（白细胞介素10），和减少促炎细胞因子水平（高迁移率组框1和肿瘤坏死因子！）。因此，H2和氧联合治疗脓毒症具有增强效应，是一种值得推荐的临床治疗脓毒症的方法。其实就是把吸氧变成联合呼吸氢气氧气混合气体可以作为治疗脓毒症的手段。
Shock. 2012 Dec;38(6):656-63. doi: 10.1097/SHK.0b013e3182758646.Combination therapy with molecular hydrogen and hyperoxia in a murine model ofpolymicrobial sepsis.Xie K, Fu W, Xing W, Li A, Chen H, Han H, Yu Y, Wang G.*Department of Anesthesiology, General Hospital of Tianjin Medical University;†Department of Colorectal and Anal Surgery, Tianjin Union Medical Center, TianjinPeople's Hospital, Tianjin; ‡Department of Dermatology, Cangzhou People'sHospital, Hebei Province, Hebei; and §Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin, People's Republic of China. ABSTRACT: Sepsis is the most common cause of death in intensive care units. Some studies have found that hyperoxia may be beneficial to sepsis. However, theclinical use of hyperoxia is hindered by concerns that it could exacerbate organ injury by increasing free radical formation. Recently, it has been suggested thatmolecular hydrogen (H2) at low concentration can exert a therapeutic antioxidant activity and effectively protect against sepsis by reducing oxidative stress.Therefore, we hypothesized that combination therapy with H2 and hyperoxia mightafford more potent therapeutic strategies for sepsis. In the present study, wefound that inhalation of H2 (2%) or hyperoxia (98%) alone improved the 14-daysurvival rate of septic mice with moderate cecal ligation and puncture (CLP) from40% to 80% or 70%, respectively. However, combination therapy with H2 andhyperoxia could increase the 14-day survival rate of moderate CLP mice to 100%and improve the 7-day survival rate of severe CLP mice from 0% to 70%. Moreover, moderate CLP mice showed significant organ damage characterized by the increases in lung myeloperoxidase activity, lung wet-to-dry weight ratio, proteinconcentration in bronchoalveolar lavage, serum biochemical parameters (alanineaminotransferase, aspartate aminotransferase, creatinine, and blood ureanitrogen), and organ histopathological scores (lung, liver, and kidney), as well as the decrease in PaO2/FIO2 ratio at 24 h, which was attenuated by either H2 or hyperoxia alone. However, combination therapy with H2 and hyperoxia had a morebeneficial effect against lung, liver, and kidney damage of moderate or severeCLP mice. Furthermore, we found that the beneficial effect of this combinationtherapy was associated with the decreased levels of oxidative product(8-iso-prostaglandin F2α), increased activities of antioxidant enzymes(superoxide dismutase and catalase) and anti-inflammatory cytokine (interleukin10), and reduced levels of proinflammatory cytokines (high-mobility group box 1and tumor necrosis factor α) in serum and tissues. Therefore, combination therapywith H2 and hyperoxia provides enhanced therapeutic efficacy via both antioxidantand anti-inflammatory mechanisms and might be potentially a clinically feasibleapproach for sepsis.
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