Excessive administration of cerulein acts through CCK receptors to stimulate hypersecretion by pancreatic acinar cells, and impairs the separation between intracellular trypsinogen and lysosomal hydrolases. These zymogens are then activated in a cathepsin B‑dependent manner, and the activated proteases further promote zymogen activation, triggering a cascade of cellular injury caused by protease activity. The inflammatory response induced by autodigestion of pancreatic tissue recruits inflammatory cells and releases inflammatory mediators, further leading to severe local or even systemic inflammatory reactions. The pathogenic factors of acute pancreatitis are relatively well understood, allowing modeling that mimics the development of human disease. However, the pathogenesis of chronic pancreatitis remains unclear. A basic modeling strategy for chronic pancreatitis is based on the principle that repeated episodes of acute pancreatitis lead to chronic pancreatitis: repeated induction of acute pancreatitis results in pathological features of chronic pancreatitis such as pancreatic fibrosis. When cerulein is used to induce pancreatitis, it is often combined with factors that increase susceptibility to pancreatitis, such as endotoxin, ethanol, hypertriglyceridemia, and others. Lipopolysaccharides (LPS) are endotoxins that activate monocytes to release cytokines and elicit systemic inflammatory responses. Clinical studies have shown that LPS levels are closely associated with the severity of acute pancreatitis. The combined use of cerulein and LPS exerts a synergistic effect in establishing pancreatitis models. LPS disrupts the normal regulatory response of inflammatory mediators, thereby progressing local pancreatitis to a severe systemic inflammatory response and exacerbating pancreatitis induced by cerulein.

C57BL/6 mice (male, 8 weeks old, weighing 18–22 g)
Modeling method: The acute pancreatitis model was successfully established by intraperitoneal injection of LPS after multiple administrations of cerulein.
Evaluation indicators: gross observation, ELISA detection, HE staining

Gross observation of pancreatic tissue

ELISA detection