关键词: 外源性, 八肽胆囊收缩素, 急性胰腺炎, 胆碱能抗炎通路, 机制

Abstract:

Objective To investigate the effect of exogenous cholecystokinin octapeptide (CCK-8) on acute pancreatitis and explore the mechanism of CCK-8 inhibiting inflammation through the cholinergic antiinflammatory pathway. Method SD rats were used to establish an acute pancreatitis model and randomly divided into four groups of 18 each: sham surgery group, model group, model preparation combined with CCK-8 group (CCK-8 group), model preparation combined with subphrenic vagus nerve transection and CCK-8 group (transection group). SD rats were euthanized in batches at 3, 6, and 9 hours in each group, and their serum interleukin-6 (IL-6) was detected using an enzyme-linked immunosorbent assay kit tumor necrosis factor (TNF)-α levels were

measured, and the pathological changes of pancreatic tissue in rats were observed. Result The serum IL-6 concentration in the sham surgery group rats was lower at various time points, while the serum IL-6 concentration in the model group rats reached a peak at 6 hours. The IL-6 concentration levels in the model group rats were higher than those in the sham surgery group rats at corresponding time points; The IL-6 concentration levels in CCK-8 group rats at 6h and 9h were significantly lower than those in the corresponding time points of the model group rats; The IL-6 concentration levels at 6h and 9h in the cut off group rats were significantly higher than those at the corresponding time points in the CCK-8 group rats, with significant differences (P ＜ 0.05). The concentration of serum TNF-α in sham operated group rats at 9 hours reaches a peak; The serum TNF-α concentration in model group rats reaches a peak at 6 hours. The concentration levels of TNF-α in model group rats at various time points were higher than the concentration levels of TNF-α in the sham surgery group rats at corresponding time points; The concentration levels of TNF-α in CCK-8 group rats is significantly lower than the concentration levels of  TNF-α in model group rats at 6h and 9h; At 6h and 9h points in the cut off group rats, the concentration levels of TNF-α is significantly higher than the concentration level of TNF-α in CCK-8 group rats at the corresponding time point, which the differences are significant(P ＜ 0.05). At 3, 6, and 9 hours, the pancreatic pathological changes in each subgroup of CCK-8 group were milder than those in the model group, while at 3, 6, and 9 hours, the pancreatic pathological changes in each subgroup of the amputation group were more severe than those in the CCK-8 group. The pancreatic tissue injury score of the sham surgery group rats was lower at various time points; The pancreatic injury score of the model group rats gradually increased over time, and the evaluation scores at each time point were higher than those of the sham surgery group rats at the corresponding time points (P ＜ 0.05); The pancreatic injury score of CCK-8 group rats showed a gradually increasing trend at various time points, and the pancreatic injury score at each time point was lower than the corresponding time point pancreatic injury score of the model group rats (P ＜ 0.05); The pancreatic injury scores of the cut off group rats were higher than those of the CCK-8 group rats at corresponding time points (P ＜ 0.05), but there was no significant difference in pancreatic injury scores compared to the model group at various time points. Conclusion CCK-8 can active the cholinergic anti-inflammatory pathway and promote the release of vagal acetylcholine, thus to participate in the regulation of inflammatory response, acute pancreatitis were reduced.

Key words: Exogeneity, Octapeptide cholecystokinin, Acute pancreatitis, Cholinergic anti-inflammatory pathway, Mechanism