# [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](https://pubmed.ncbi.nlm.nih.gov/29920028/)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 2%

## Delivery context

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.

## Safety notes

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:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [LFL / UFL terminology](https://h2-papers.org/en/safety-notes/lfl-ufl-explained)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 29920028. https://h2-papers.org/en/papers/29920028
> **Source**: PubMed PMID [29920028](https://pubmed.ncbi.nlm.nih.gov/29920028/)