Development of a novel rat model for pancreaticoduodenectomy.

Pancreaticoduodenectomy (PD) is a complex surgical procedure associated with substantial postoperative risk. Despite its clinical significance, the lack of a standardized, cost-effective animal model hinders mechanistic research. Here, we aimed to establish a feasible and safe rat PD model. A simulated PD procedure was performed on Sprague-Dawley rats, including pancreaticojejunostomy (PJ), hepatojejunostomy (HJ), and gastrojejunostomy (GJ). The survival rate, surgical details, enzyme levels (amylase and lipase) and histopathological changes were analyzed. 7-day survival rate was 85.0% (51/60, 95% CI 0.739-0.919). The mean operation duration was 74.9 ± 12.3 min (PJ: 10.0 ± 2.8 min; HJ: 9.7 ± 3.9 min; GJ: 14.8 ± 4.9 min). Histological analysis revealed pancreatic injury at postoperative day (POD) 1, transient acinar-to-ductal metaplasia (ADM) at POD3 and restoration of acinar architecture by POD 7. Immunohistochemistry (IHC) staining demonstrated early acinar apoptosis (C-caspase-3) at POD1-3, CK19 upregulation with reduced amylase at POD3, and re-emergence of acinar markers (amylase) by POD7. Postoperative serum and ascites amylase/lipase levels were statistically elevated and recovered around day 5. This study successfully established a stable and economical rat PD model, providing a practical platform for postoperative mechanistic studies.