WOFAPS 2025 8th World Congress of Pediatric Surgery

Yihang Yang, Chunbao Guo

chongqing health center for women and children

This study investigates the role of Gasdermin D (GSDMD) in macrophage pyroptosis and its impact on intestinal injury in necrotizing enterocolitis (NEC), a severe gastrointestinal emergency in neonates. The research aims to elucidate the mechanisms underlying GSDMD-dependent pyroptosis and its contribution to inflammation and intestinal damage in NEC.

Research Background

NEC is a leading cause of gastrointestinal emergencies in neonates, characterized by intestinal inflammation and necrosis. The pathogenesis of NEC is largely attributed to heightened macrophage inflammasome activity, leading to pyroptosis and cytokine release. GSDMD is a key mediator of pyroptosis, facilitating the formation of membrane pores and the release of pro-inflammatory cytokines like IL-1β. However, the specific role of GSDMD in NEC remains unclear.

Methods

The study analyzed human intestinal samples from infants with NEC and used a mouse model to investigate the effects of GSDMD deficiency and pharmacological inhibition with disulfiram on NEC development. Intestinal tissues were examined for GSDMD expression, macrophage infiltration, and inflammatory markers. Bone marrow-derived macrophages (BMDMs) were used to assess pyroptosis and cytokine release.

Results

GSDMD expression was significantly elevated in the intestines of NEC patients. GSDMD deficiency in mice delayed NEC onset, reduced intestinal macrophage infiltration, and improved survival rates. Disulfiram treatment similarly mitigated NEC severity by inhibiting GSDMD pore formation, reducing IL-1β release, and enhancing macrophage antibacterial activity.

Conclusions

The study demonstrates that GSDMD plays a critical role in macrophage pyroptosis and intestinal injury in NEC. Targeting GSDMD with disulfiram could be a potential therapeutic strategy to reduce inflammation and improve outcomes in NEC. Future research should focus on further exploring the mechanisms of GSDMD in NEC and its potential as a therapeutic target.