Abstract: BACKGROUND: Establishing a stable and reliable animal model of acute pancreatitis is of great significance for understanding its pathogenesis, pathophysiological characteristics, and clinical medication. Domestic and foreign studies have shown that cerulein, L-arginine, and sodium taurocholate can induce acute pancreatitis, but their pathophysiological characteristics and model characteristics are still unclear.
OBJECTIVE: To establish an acute pancreatitis rat model using cerulein, L-arginine, and sodium taurocholate and to observe the changing patterns of model features at different time points.
METHODS: Ninety-six healthy male Sprague-Dawley rats were randomly divided into normal group, cerulein group, L-arginine group, and sodium taurocholate group, with 24 rats in each group. Within each group, there were three subgroups (n=8 per group): 12-, 24-, and 48-hour subgroups. Cerulein was administered via intraperitoneal injection six times with a 1-hour interval. L-arginine was administered through two intraperitoneal injections with a 1-hour interval. Sodium taurocholate was injected for inducing acute pancreatitis models through retrograde injection into the bile-pancreatic duct. By examining the rat survival rate, gross morphology of the pancreas, calculating the pancreatic organ index, and measuring levels of amylase, lipase, alanine transaminase, aspartate transaminase, blood urea nitrogen, and creatinine, as well as observing pancreatic tissue pathological features through hematoxylin-eosin staining and conducting a pancreatic injury scoring, we evaluated the changing patterns of model features at different time points.
RESULTS AND CONCLUSION: Compared with the normal group, the overall survival rate of rats was 100% in the cerulein group, 88% in the L-arginine group, and 96% in the sodium taurocholate group. The pancreatic organ index was increased in all groups. Gross observation indicated that, In the cerulein group, pancreatic edema, blurred lobes, and looseness were visible. In the L-arginine group, the pancreatic glands were enlarged and thickened with patchy bleeding. In the sodium taurocholate group, pancreatic tissue showed varying degrees of congestion and edema accompanied by scattered flakes of hemorrhage and necrosis. The levels of serum alanine transaminase, aspartate transaminase, blood urea nitrogen, creatinine, amylase, and lipase in rats exhibited consistent changes. In the cerulein group, these parameters possibly peaked at 12 hours (P < 0.05) and then showed a declining trend. In the L-arginine group, they reached the highest levels at 24 hours (P < 0.05) and significantly decreased at 48 hours. In the sodium taurocholate group, serum amylase and lipase remained at higher levels at 12 hours with a slow decline trend (P < 0.05). Compared with the normal group, microscopic examination revealed mild acinar edema and widened interlobular spaces in the cerulein group, with a higher presence of inflammatory cells. In the L-arginine group, there was widening of interlobular spaces, extensive infiltration of inflammatory cells, and patchy necrotic areas. In the sodium taurocholate group, significant pancreatic edema, structural disarray, extensive necrotic foci, and inflammatory cell infiltration were observed. Compared with the normal group, the pathological scores of induced acute pancreatitis in all three models were significantly different at each time point (P < 0.05). Moreover, the pathological scores in each group increased over time, indicating a gradual worsening of pancreatic tissue damage. When comparing different models at the same time, there were differences in pathological scores, with the sodium taurocholate group having the highest scores, followed by the L-arginine group, and the cerulein group having the lowest scores. Analyzing the three models at the same time point, the most severe condition was in the sodium taurocholate group, which was characterized by pancreatic hemorrhage and necrosis, followed by the L-arginine group, which was characterized by necrosis, and the least severe condition was in the cerulein group, mainly characterized by edema. The serum biochemical index levels of the cerulein and L-arginine groups decreased at 48 hours, indicating that these two models may have a tendency to self-heal and belong to a self-limiting disease course. The serum biochemical index levels of the sodium taurocholate group decreased slowly after 12 hours. Therefore, pancreatic injury in the sodium taurocholate group might not be relieved after 48 hours or longer.

Key words: cerulein, L-arginine, sodium taurocholate, acute pancreatitis, animal model, comparative study