高濃度水素ガス吸入によるLPS誘発急性肺傷害の軽減とNrf2シグナル経路の関与
The lung is among the earliest organs to sustain damage during sepsis. This study examined whether inhalation of 67% high-concentration hydrogen (HCH) could reduce acute lung injury (ALI) induced by lipopolysaccharide (LPS) aerosol in mice, and whether the Nrf2 signaling pathway mediates this effect. HCH was administered for 1 hour at 1 and 6 hours post-LPS exposure. Lung tissue and bronchoalveolar lavage fluid (BALF) were collected at 4 and 24 hours. Histological scores, wet/dry weight ratios, myeloperoxidase (MPO) activity, BALF protein and cytokine levels, caspase-3 activity, TUNEL-positive cell counts, and Nrf2/NF-κB expression were measured in both wild-type and Nrf2-knockout mice. HCH inhalation markedly reduced pathological lung damage, inflammatory cytokine levels, MPO activity, and apoptotic cell counts. Critically, these protective effects were absent in Nrf2-knockout animals, indicating that Nrf2 activation is essential for HCH-mediated protection against LPS-induced ALI.
HCH inhalation activates the Nrf2 signaling pathway, which in turn suppresses NF-κB-mediated pro-inflammatory cytokine production and caspase-3-dependent apoptosis, thereby reducing LPS-induced pulmonary damage.
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.
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https://h2-papers.org/en/papers/34634688