敗血症マウスの肺組織におけるHMGB1放出に対する水素ガスの抑制効果：Nrf2/HO-1経路を介したメカニズムの検討
Using a cecal ligation and puncture (CLP) sepsis model in wild-type and Nrf2-knockout ICR mice, the effects of 2% H2 gas inhalation (60 min at 1 h and 6 h post-surgery) on lung injury were examined. In wild-type animals, H2 inhalation improved 7-day survival, reduced the lung wet/dry weight ratio and histopathological injury scores, lowered pro-inflammatory mediators (TNF-α, IL-6, HMGB1), elevated the anti-inflammatory cytokine IL-10, enhanced antioxidant enzymes (SOD, CAT, HO-1), and decreased the oxidative marker MDA. These protective outcomes were absent in Nrf2-knockout mice, indicating that Nrf2 is essential for H2-mediated upregulation of HO-1 and downregulation of HMGB1, thereby attenuating sepsis-induced pulmonary damage.
H2 gas activates Nrf2, which upregulates HO-1 expression and suppresses HMGB1 release, leading to reduced oxidative stress and pro-inflammatory cytokine levels that collectively mitigate sepsis-induced lung injury.
For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.
See also:
https://h2-papers.org/en/papers/30660872