Sakata Hiroyuki, Okamoto Ayana, Aoyama-Ishikawa Michiko, Yamashita Hayato, Kohama Keisuke, Fujisaki Noritomo, Yamada Taihei, Kotani Joji, Tsukahara Kohei, Iida Atsuyoshi, Nakao Atsunori
Department of Emergency Disaster and Critical Care Medicine Hyogo College of Medicine Nishinomiya Hyogo Japan.
Kobe University Graduate School of Health Science Kobe Hyogo Japan.
Acute Med Surg. 2016 Jun 14;4(1):38-45. doi: 10.1002/ams2.218. eCollection 2017 Jan.
Gastrointestinal dysmotility frequently occurs during sepsis and multiple organ failure, remaining a major cause of morbidity and mortality in critically ill patients. Previous studies have shown that hydrogen, a new therapeutic gas, can improve various organ damage associated with sepsis. In this study, we investigated the protective efficacies of inhaled hydrogen against lipopolysaccharide (LPS)-induced ileus.
Sepsis was induced in rats and mice by a single i.p. injection of LPS at 15 mg/kg for mice and 5 mg/kg for rats. Four groups of rats and mice including sham/air, sham/hydrogen, LPS/air, and LPS/hydrogen were analyzed. Hydrogen (1.3%) was inhaled for 25 h beginning at 1 h prior to LPS treatment. Gastrointestinal transit was quantified and cytokine levels, as well as neutrophil extravasation, in the intestinal muscularis propria were determined.
Lipopolysaccharide challenge remarkably delayed gastrointestinal transit of non-absorbable dextran, associated with increased leukocyte recruitment and upregulation of pro-inflammatory cytokine mRNA expressions in the muscularis propria. Hydrogen significantly prevented LPS-induced bowel dysmotility and reduced leukocyte extravasation, as well as inhibition of inflammatory cytokine expression. analysis of cytokine levels after LPS treatment of cultured macrophages showed an increase of interleukin-10 by hydrogen regardless of the presence of nitric oxide.
This study showed the protective effects of hydrogen inhalation on LPS-induced septic ileus through inhibition of inflammation in the muscularis propria. These inhibitory effects on the pro-inflammatory response may be partially derived from anti-inflammatory cytokine interleukin-10 induction.
胃肠道动力障碍在脓毒症和多器官功能衰竭期间经常发生，仍然是危重症患者发病和死亡的主要原因。先前的研究表明，氢气作为一种新型治疗性气体，可以改善与脓毒症相关的各种器官损伤。在本研究中，我们研究了吸入氢气对脂多糖（LPS）诱导的肠梗阻的保护作用。
通过腹腔注射LPS诱导大鼠和小鼠脓毒症，小鼠剂量为15mg/kg，大鼠剂量为5mg/kg。分析四组大鼠和小鼠，包括假手术/空气组、假手术/氢气组、LPS/空气组和LPS/氢气组。在LPS处理前1小时开始吸入氢气（1.3%），持续25小时。对胃肠道转运进行定量分析，并测定肠固有肌层中的细胞因子水平以及中性粒细胞渗出情况。
脂多糖攻击显著延迟了不可吸收葡聚糖的胃肠道转运，这与白细胞募集增加和固有肌层中促炎细胞因子mRNA表达上调有关。氢气显著预防了LPS诱导的肠道动力障碍，减少了白细胞渗出，并抑制了炎性细胞因子表达。对培养的巨噬细胞进行LPS处理后的细胞因子水平分析表明，无论是否存在一氧化氮，氢气均可使白细胞介素-10增加。
本研究表明，吸入氢气通过抑制固有肌层炎症对LPS诱导的脓毒症性肠梗阻具有保护作用。这些对促炎反应的抑制作用可能部分源自抗炎细胞因子白细胞介素-10的诱导。
