Verifying inflammation and pancreatic blood flow in a mouse model of post-endoscopic retrograde cholangiopancreatography

Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is thought to be exacerbated by pancreatic ischemia caused by excessive pancreatic ductography. However, its exact mechanism is unknown. In this study, a mouse model of PEP was developed to examine the effects of pancreatic ductography on pancreatic microcirculation. Investigating the mechanisms of cell death in acinar cells, we also aimed to verify the correlation between microcirculation changes and PEP exacerbation. Fluorescence vascular pancreatic duct imaging and pathological studies revealed that the injected contrast medium leaked into the interstitium, compressing the blood vessels and inducing pancreatic ischemia. This ischemia spread around the large blood vessels, with hypoxia-inducible factor (HIF-1α) expressed in the affected acinar cells. Consequently, the acinar cells collapsed, macrophages accumulated around them, and necroptosis was induced. These findings suggest that pancreatic ductography can disrupt microcirculation, induce necroptosis, and exacerbate PEP. Controlling tissue hypoxia and necroptosis in human PEP could potentially prevent exacerbation.