Gouty arthritis is a common inflammatory arthritis caused by the deposition of monosodium urate (MSU) crystals, closely associated with the overactivation of the NLRP3 inflammasome and oxidative stress. Hydrogen, a selective antioxidant, exhibits anti-inflammatory effects in various diseases, but its specific regulatory mechanism regarding the NLRP3 inflammasome in gouty arthritis remains unclear. This study aims to investigate the inhibitory effects of hydrogen on NLRP3 inflammasome activation in gouty arthritis and explore the underlying mechanisms through in vitro and in vivo experiments.

For in vitro experiments, primary mouse bone marrow-derived macrophages (BMDMs) were divided into three groups: blank control, MSU-induced (LPS+MSU), and hydrogen-treated (LPS+MSU+hydrogen-rich medium). Western blot was used to detect the protein expression of pro-caspase-1, caspase-1, pro-IL-1β, and IL-1β. ELISA was employed to measure the levels of IL-1β, IL-18, and TNF-α in the supernatant. Oxidative stress markers, including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), total antioxidant capacity (T-AOC), and xanthine oxidase (XOD), were assessed using colorimetric assays. For in vivo experiments, a mouse air pouch model and a gouty arthritis paw model were established. C57BL/6 mice were divided into blank control, MSU model, and hydrogen-treated (hydrogen-rich water) groups. Exudate from the air pouch or homogenates from paw tissue were collected for analysis via Western blot, ELISA, and oxidative stress assays.

In vitro, compared to the MSU-induced group, the hydrogen-treated group showed significantly reduced protein expression of caspase-1 (p10) and IL-1β in BMDMs. The levels of IL-1β, IL-18, and TNF-α in the supernatant were also significantly decreased (P<0.05). Additionally, hydrogen treatment significantly increased the levels of SOD, GSH-Px, and T-AOC while decreasing XOD activity (P<0.05). Consistent with these findings, in vivo results from both the air pouch model and the gouty arthritis model demonstrated that hydrogen intervention significantly reduced the expression of caspase-1 and IL-1β, decreased the levels of inflammatory factors (P<0.05), and alleviated oxidative stress in the exudate and paw tissue homogenates.

This study confirms that hydrogen exerts protective effects in gouty arthritis by inhibiting MSU crystal-induced NLRP3 inflammasome activation, reducing the release of inflammatory cytokines, and ameliorating oxidative stress. These findings provide experimental evidence supporting hydrogen as a potential therapeutic strategy for gouty arthritis, though further research is warranted to validate its clinical application.