Single Atom Catalysts Ameliorate Sepsis Induced Intestinal Barrier Damage

Sepsis often leaded to severe intestinal mucosal barrier injury, involving multiple pathological links such as macrophage polarization imbalance, gut microbiota dysbiosis, and metabolic disorders. However, the underlying mechanisms of intestinal injury in sepsis are not fully understood, and developing new therapeutic strategies is challenging. Vanadium-based single-atom catalysts have shown promise in intervening inflammatory diseases due to their excellent redox catalytic properties, but their protective effects and mechanisms in septic intestinal injury remain unexplored. In this study, two single-atom catalysts, V-N4 and V-N3P, with precise coordination environments were synthesized. A series of experiments were conducted using in vivo (pig and mouse sepsis models established by cecal ligation and puncture) and in vitro approaches. Methods such as 16S rRNA sequencing, liquid chromatograph mass spectrometer analysis, transmission electron microscopy, immunohistochemistry, Western blot, and flow cytometry were employed. Results showed that V-N3P had a unique V-N3P coordination structure, and its antioxidant nanozyme activity was enhanced through phosphorus-induced charge delocalization, being more effective than V-N4 in scavenging reactive oxygen species.