水素ガス吸入によるPINK1/Parkin経路を介したミトファジー調節と脳虚血再灌流障害の軽減：SH-SY5Y細胞およびマウスを用いた検討
This study examined the effects of molecular hydrogen (H₂) inhalation on cerebral ischemia-reperfusion injury (CIRI) using both a mouse middle cerebral artery occlusion/reperfusion (MCAO/R) model and human neuroblastoma SH-SY5Y cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). In vivo, H₂ inhalation reduced infarct volume, improved neurological deficit scores, decreased histopathological damage, and suppressed neuronal apoptosis while promoting mitophagy. In OGD/R-exposed SH-SY5Y cells, H₂ enhanced cell viability, lowered mitochondrial reactive oxygen species, preserved mitochondrial membrane potential, and activated the PINK1/Parkin mitophagy pathway. Concurrently, the Nrf2/HO-1 antioxidant axis was upregulated and NF-κB-driven inflammatory signaling was attenuated. Pretreatment with the Nrf2-specific inhibitor ML385 (5 μM) substantially reversed these mitochondrial protective and anti-apoptotic outcomes, indicating that Nrf2 activation is integral to H₂-mediated neuroprotection against CIRI.
H₂ activates the PINK1/Parkin pathway to promote selective clearance of damaged mitochondria (mitophagy), upregulates the Nrf2/HO-1 antioxidant axis, and suppresses NF-κB inflammatory signaling, collectively reducing oxidative stress and neuronal apoptosis in ischemia-reperfusion conditions.
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/42049119