(128) Prostaglandin Metabolic Dysregulation in Necroptosis Promotes Ferroptosis to Exacerbate Abdominal Sepsis

Introduction/Rationale: Severe intra-abdominal infection, often complicated by sepsis or septic shock, is a life-threatening condition requiring immediate surgical intervention. According to our previous study, intra-abdominal sepsis arises from postoperative complications, trauma or acute abdominal conditions, leading to a systemic inflammatory response that progressively damages multiple organs.
Among the various organs affected by intra-abdominal sepsis, the intestine plays a central role as the initiating organ. The intestinal epithelial barrier is highly vulnerable to systemic inflammation and hypoxia, which exacerbates barrier dysfunction, promoting bacterial translocation and further aggravating systemic inflammation. This creates a vicious cycle, worsening the patient’s condition and increasing mortality risk.

Methods: 1. RNA Sequencing and Bioinformatics Analysis:
2. Western Blot (WB) Analysis:
3. ELISA for Prostaglandin E₂ (PGE₂) and Inflammatory Cytokines​

Results: By elucidating the interactions between necroptosis, ferroptosis and metabolic dysregulation in the intestinal epithelium, we aim to uncover potential therapeutic targets that could help preserve intestinal barrier integrity and ultimately improve survival in intra-abdominal sepsis patients.

Conclusion: A key question is whether metabolic dysregulation following necroptosis exacerbates inflammation and promotes additional cell death pathways such as ferroptosis, thereby worsening intra-abdominal sepsis-induced intestinal injury. If so, targeting these metabolic changes could provide new therapeutic strategies to mitigate intestinal epithelial damage and improve patient outcomes. Identifying novel intervention targets based on these mechanisms may offer a promising direction for intra-abdominal sepsis treatment.