Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine at the Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Antioxid Redox Signal. 2012 Jul 1;17(1):11-21. doi: 10.1089/ars.2011.4363.
The role of hydrogen sulfide (H(2)S) in endotoxin (lipopolysaccharide [LPS])-induced inflammation is incompletely understood. We examined the impact of H(2)S breathing on LPS-induced changes in sulfide metabolism, systemic inflammation, and survival in mice.
Mice that breathed air alone exhibited decreased plasma sulfide levels and poor survival rate at 72 h after LPS challenge. Endotoxemia markedly increased alanine aminotransferase (ALT) activity and nitrite/nitrate (NOx) levels in plasma and lung myeloperoxidase (MPO) activity in mice that breathed air. In contrast, breathing air supplemented with 80 ppm of H(2)S for 6 h after LPS challenge markedly improved survival rate compared to mice that breathed air alone (p<0.05). H(2)S breathing attenuated LPS-induced increase of plasma ALT activity and NOx levels and lung MPO activity. Inhaled H(2)S suppressed LPS-induced upregulation of inflammatory cytokines, while it markedly induced anti-inflammatory interleukin (IL)-10 in the liver. Beneficial effects of H(2)S inhalation after LPS challenge were associated with restored sulfide levels and markedly increased thiosulfate levels in plasma. Increased thiosulfate levels after LPS challenge were associated with upregulation of rhodanese, but not cystathionine-γ-lyase (CSE), in the liver. Administration of sodium thiosulfate dose-dependently improved survival after LPS challenge in mice.
By measuring changes in plasma levels of sulfide and sulfide metabolites using an advanced analytical method, this study revealed a critical role of thiosulfate in the protective effects of H(2)S breathing during endotoxemia.
These observations suggest that H(2)S breathing prevents inflammation and improves survival after LPS challenge by altering sulfide metabolism in mice.
硫化氢（H2S）在脂多糖（LPS）诱导的炎症中的作用尚不完全清楚。我们研究了 H2S 呼吸对 LPS 诱导的硫化物代谢、全身炎症和小鼠存活率变化的影响。
单独呼吸空气的小鼠在 LPS 攻击后 72 小时表现出血浆硫化物水平降低和生存率差。内毒素血症显著增加了呼吸空气的小鼠血浆中天冬氨酸转氨酶（ALT）活性和亚硝酸盐/硝酸盐（NOx）水平以及肺髓过氧化物酶（MPO）活性。相比之下，在 LPS 攻击后呼吸 80ppm 的 H2S 6 小时可显著提高生存率，与单独呼吸空气的小鼠相比（p<0.05）。H2S 呼吸可减弱 LPS 诱导的血浆 ALT 活性和 NOx 水平以及肺 MPO 活性的增加。吸入 H2S 可抑制 LPS 诱导的促炎细胞因子上调，同时可显著诱导肝脏抗炎细胞因子白细胞介素（IL）-10。LPS 攻击后 H2S 吸入的有益作用与硫化物水平的恢复和血浆中硫代硫酸盐水平的显著增加有关。LPS 攻击后硫代硫酸盐水平的增加与肝脏中 rhodanese 的上调有关，但与 cystathionine-γ-lyase（CSE）无关。硫代硫酸钠的剂量依赖性给药可提高 LPS 攻击后小鼠的生存率。
通过使用先进的分析方法测量血浆中硫化物和硫化物代谢物水平的变化，本研究揭示了硫代硫酸盐在 H2S 呼吸对内毒素血症期间的保护作用中的关键作用。
这些观察结果表明，H2S 呼吸通过改变小鼠的硫化物代谢来预防 LPS 攻击后的炎症和提高生存率。
