Development of a novel rat model for pancreaticoduodenectomy

Abstract

Abstract 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.