[Role of Rho/ROCK signaling pathway in the protective effects of hydrogen against acute lung injury in septic mice].
敗血症マウスの急性肺傷害に対する水素吸入の保護効果におけるRho/ROCKシグナル経路の関与
Abstract
Using a cecal ligation and puncture (CLP) sepsis model in 80 male C57BL/6 mice, this study examined the effects of 2% H2 inhalation administered for 1 hour at 1 and 6 hours post-CLP. At 24 hours, H2-treated animals showed marked reductions in bronchoalveolar lavage fluid protein, TNF-α, IL-1β, and polymorphonuclear neutrophil counts compared with untreated septic controls. Pulmonary Evans blue dye extravasation, malondialdehyde content, and wet/dry weight ratio were also significantly lower, while superoxide dismutase activity and ZO-1 tight-junction protein expression were elevated. Rho/ROCK pathway activation markers—Rho-GTP/total Rho ratio, ROCK1 and ROCK2 expression, and p-MYPT1/MYPT1 ratio—were all suppressed by H2 inhalation. Histological examination confirmed attenuation of lung tissue damage. These findings indicate that H2 inhalation reduces pulmonary endothelial permeability, inflammatory mediator release, and oxidative stress in sepsis-induced acute lung injury through downregulation of the Rho/ROCK signaling cascade.
Mechanism
H2 inhalation suppresses Rho-GTP activation, reducing ROCK1/ROCK2 expression and MYPT1 phosphorylation, thereby preserving endothelial tight-junction protein ZO-1, attenuating neutrophil infiltration, and decreasing oxidative stress markers in septic lung tissue.
Bibliographic
- Authors
- Zhang H, Liu L, Sun Z, Liang Y, Yu Y
- Journal
- Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
- Year
- 2016
- PMID
- 29920028
Tags
Delivery context
In air, molecular hydrogen is reported to be combustible across approximately **4% (LFL, lower flammability limit) to 75% (UFL, upper flammability limit)**. Among high-concentration hydrogen inhalers, 66% output sits inside this range, and even pure-hydrogen (100%) output forms a 4–75% concentration-gradient layer at the device–air boundary (the UFL 75% paradox). Engineering principle would therefore call for operation below LFL (the classical 4%); that figure, however, was measured under closed, pre-mixed, static conditions. For the open, dynamic inhalation environment, the empirical value reported in the literature is **10%**, which is the figure referenced in practice as the operating ceiling. The 66% / 100% output devices are recorded in the Japanese Consumer Affairs Agency accident-information database, and from these considerations are not recommended.
Safety notes
See also: