Li Yuan, Li Qi, Chen Hongguang, Wang Tao, Liu Lingling, Wang Guolin, Xie Keliang, Yu Yonghao
*Department of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin, China; †Tianjin Institute of Anesthesiology, Tianjin, China; ‡Department of Cardiology, Tianjin People's Hospital, Tianjin, China; and §Department of Anesthesiology, Tianjin Chest Hospital, Tianjin, China.
Shock. 2015 Jul;44(1):90-8. doi: 10.1097/SHK.0000000000000382.
Hydrogen gas (H2) has antioxidative, anti-inflammatory, and antiapoptotic effects and may have beneficial effects in severe sepsis. The purpose of this study was to investigate the mechanisms underlying these protective effects. Male Institute for Cancer Research mice were randomized into 6 groups: sham; sham + H2; severe sepsis; severe sepsis + H2; severe sepsis + zinc protoporphyrin IX (ZnPPIX), a heme oxygenase-1 (HO-1) inhibitor; and severe sepsis + H2 + ZnPPIX. Cecal ligation and puncture (CLP) was used to induce sepsis. Mice in the H2 groups received inhaled 2% H2 for 1 h at 1 h and 6 h after CLP or sham operation. Mice in the ZnPPIX groups received 40-mg/kg ZnPPIX by intraperitoneal injection 1 h before CLP. Tin protoporphyrin IX (TinPPIX), another HO-1 inhibitor, was also used in part for this study. Mice in the TinPPIX groups received 50-mg/kg TinPPIX through subcutaneous injection 6 h before CLP. The levels of biochemical markers, oxidative products, inflammatory mediator, the number of intestinal apoptotic cells, and the colony-forming unit numbers in the peritoneal lavage fluid were much higher in the severe sepsis group compared with the sham group. Intestinal injury in animals with severe sepsis was worse than that in animals in the sham group. H2 therapy in the animals with severe sepsis was associated with reduced intestinal injury, decreased numbers of colony-forming unit and apoptotic cells, reduced levels of biochemical markers, oxidative products, and high-mobility group box 1 protein. The protective effects of H2 were reversed by ZnPPIX and TinPPIX. Protein and messenger RNA expressions of HO-1 and nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) in the intestine were increased in the severe sepsis group compared to the sham group, and H2 further increased their expressions in the severe septic mice. Zinc protoporphyrin IX and TinPPIX inhibited the expression of HO-1 protein. Hydrogen has the capacity to protect mice from organ injury in severe sepsis through a mechanism involving HO-1.
氢气（H₂）具有抗氧化、抗炎和抗凋亡作用，可能对严重脓毒症有有益影响。本研究的目的是探讨这些保护作用的潜在机制。将雄性癌症研究所小鼠随机分为6组：假手术组；假手术 + H₂组；严重脓毒症组；严重脓毒症 + H₂组；严重脓毒症 + 锌原卟啉IX（ZnPPIX）组，锌原卟啉IX是一种血红素加氧酶-1（HO-1）抑制剂；严重脓毒症 + H₂ + ZnPPIX组。采用盲肠结扎穿孔术（CLP）诱导脓毒症。H₂组小鼠在CLP或假手术后1小时和6小时吸入2% H₂ 1小时。ZnPPIX组小鼠在CLP前1小时腹腔注射40 mg/kg ZnPPIX。本研究部分还使用了另一种HO-1抑制剂锡原卟啉IX（TinPPIX）。TinPPIX组小鼠在CLP前6小时皮下注射50 mg/kg TinPPIX。与假手术组相比，严重脓毒症组的生化标志物、氧化产物、炎症介质水平、肠道凋亡细胞数量以及腹腔灌洗液中的菌落形成单位数量要高得多。严重脓毒症动物的肠道损伤比假手术组动物更严重。严重脓毒症动物接受H₂治疗与肠道损伤减轻、菌落形成单位和凋亡细胞数量减少、生化标志物、氧化产物和高迁移率族蛋白B1水平降低有关。ZnPPIX和TinPPIX可逆转H₂的保护作用。与假手术组相比，严重脓毒症组肠道中HO-1和核因子红细胞2 p45相关因子2（Nrf2）的蛋白质和信使核糖核酸表达增加，H₂进一步增加了严重脓毒症小鼠中它们的表达。锌原卟啉IX和TinPPIX抑制HO-1蛋白的表达。氢气能够通过涉及HO-1的机制保护小鼠免受严重脓毒症中的器官损伤。
