Fig. 8

Aseptic inflammation caused by acinar cell injury leads to local tissue hypoxia. The hypoxic environment causes a decrease in the mitochondrial membrane potential of pancreatic stellate cells and the release of reactive oxygen species. Reactive oxygen species activate the NF-κB signaling pathway, and the nuclear entry of pP65 increases. On the one hand, pP65 directly binds to the promoter region of HIF-1α to promote the expression of HIF-1α. On the other hand, pP65 can inhibit the expression of PHD2, thereby blocking the ubiquitination and degradation of HIF-1α by PHD2, ultimately leading to the accumulation of HIF-1α in cells. HIF-1α can promote glycolysis and lead to the activation of PSCs to release cytokines such as CXCL1, thereby chemotactically attracting the infiltration of neutrophils and aggravating AP