Institute of Surgical Research, Department of Biochemistry, University of Szeged, Szeged, Hungary.
Crit Care Med. 2012 Apr;40(4):1269-78. doi: 10.1097/CCM.0b013e31823dae05.
Gastrointestinal methane generation has been demonstrated in various stress conditions, but it is not known whether nonasphyxiating amounts have any impact on the mammalian pathophysiology. We set out to characterize the effects of exogenous methane administration on the process of inflammatory events arising after reoxygenation in a large animal model of ischemia-reperfusion.
A randomized, controlled in vivo animal study.
A university research laboratory.
Inbred beagle dogs (12.7 6 2 kg).
Sodium pentobarbital-anesthetized animals were randomly assigned to sham-operated or ischemia-reperfusion groups, where superior mesenteric artery occlusion was maintained for 1 hr and the subsequent reperfusion was monitored for 3 hrs. For 5 mins before reperfusion, the animals were mechanically ventilated with normoxic artificial air with or without 2.5% methane. Biological responses to methane-oxygen respirations were defined in pilot rat studies and assay systems were used with xanthine oxidase and activated canine granulocytes to test the in vitro bioactivity potential of different gas concentrations.
The macrohemodynamics and small intestinal pCO(2) gap changes were recorded and peripheral blood samples were taken for plasma nitrite/nitrate and myeloperoxidase analyses. Tissue superoxide and nitrotyrosine levels and myeloperoxidase activity changes were determined in intestinal biopsy samples; structural mucosal damage was measured by hematoxylin and eosin staining. Methane inhalation did not influence the macrohemodynamics but significantly reduced the magnitude of the tissue damage and the intestinal pCO(2) gap changes after reperfusion. Furthermore, the plasma and mucosal myeloperoxidase activity and the intestinal superoxide and nitrotyrosine levels were reduced, whereas the plasma nitrite/nitrate concentrations were increased. Additionally, methane effectively and specifically inhibited leukocyte activation in vitro.
These data demonstrate the anti-inflammatory profile of methane. The study provides evidence that exogenous methane modulates leukocyte activation and affects key events of ischemia-reperfusion-induced oxidative and nitrosative stress and is therefore of potential therapeutic interest in inflammatory pathologies.
在各种应激条件下已证实胃肠道会产生甲烷，但非窒息量的甲烷是否会对哺乳动物的病理生理学产生影响尚不清楚。我们旨在描述外源性甲烷给药对缺血再灌注大型动物模型复氧后炎症事件发生过程的影响。
随机、对照的体内动物研究。
大学研究实验室。
近交系比格犬（12.762 千克）。
用戊巴比妥钠麻醉动物，随机分配至假手术或缺血再灌注组，其中肠系膜上动脉阻塞 1 小时，随后再灌注 3 小时。在再灌注前 5 分钟，动物用正常氧人工空气进行机械通气，或用 2.5%甲烷进行通气。甲烷-氧呼吸的生物学反应在大鼠试验中进行了定义，并使用黄嘌呤氧化酶和激活的犬嗜中性粒细胞检测不同气体浓度的体外生物活性潜力。
记录宏观血流动力学和小肠 pCO2 间隙变化，并采集外周血样以分析血浆硝酸盐/亚硝酸盐和髓过氧化物酶。测定肠活检样本中的组织超氧化物和硝基酪氨酸水平以及髓过氧化物酶活性变化；通过苏木精和伊红染色测量黏膜结构损伤。甲烷吸入不影响宏观血流动力学，但显著降低再灌注后组织损伤和小肠 pCO2 间隙变化的幅度。此外，降低了血浆和黏膜髓过氧化物酶活性以及肠组织超氧化物和硝基酪氨酸水平，而血浆硝酸盐/亚硝酸盐浓度增加。此外，甲烷在体外能有效且特异性地抑制白细胞的激活。
这些数据表明甲烷具有抗炎作用。研究结果表明，外源性甲烷调节白细胞激活，并影响缺血再灌注诱导的氧化和硝化应激的关键事件，因此在炎症性疾病中具有潜在的治疗意义。
