マウス褥瘡モデルにおける皮膚虚血再灌流傷害に対する水素ガス吸入の保護効果
Using a mouse model of repetitive cutaneous ischaemia/reperfusion (I/R) injury that mimics pressure ulcer formation, this study examined the effects of molecular hydrogen (H2) gas inhalation. H2 inhalation significantly reduced wound area, oxidative DNA damage (8-oxo-dG levels), and apoptosis rates in skin lesions. ROS accumulation was suppressed while antioxidant enzyme activities were enhanced through upregulation of Nrf2 and its downstream components in wound tissue and H2O2-treated endothelial cells. Endothelial overexpression of MCP-1, E-selectin, P-selectin, and ICAM-1 was attenuated, and infiltration of inflammatory cells along with production of TNF-α, IL-1, IL-6, and IL-8 was reduced. Concurrently, pro-healing mediators including IL-22, TGF-β, VEGF, and IGF1 were upregulated, MMP9 production was suppressed, and cutaneous collagen synthesis was accelerated. These findings indicate that H2 inhalation suppresses pressure ulcer development through coordinated antioxidant, anti-inflammatory, and wound-healing mechanisms.
H2 activates the Nrf2 pathway to enhance antioxidant enzyme activity and reduce ROS, suppresses endothelial adhesion molecules (MCP-1, E-selectin, P-selectin, ICAM-1) and pro-inflammatory cytokines (TNF-α, IL-1, IL-6, IL-8), upregulates pro-healing factors (IL-22, TGF-β, VEGF, IGF1), and inhibits MMP9 to promote collagen synthesis.
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/29921037