Demcsák Alexandra, Tran Thanh, Sahin-Tóth Miklós, Geisz-Fremy Andrea
Department of Surgery, University of California Los Angeles, Los Angeles, CA, 90095, USA.
Department of Surgery, Boston University, 700 Albany Street, W408G, Boston, MA, 02118, USA.
Sci Rep. 2025 May 8;15(1):16030. doi: 10.1038/s41598-025-98914-z.
Hyperstimulation with the secretagogue cerulein is a commonly used experimental model to study acute, recurrent acute and chronic pancreatitis in mice. Earlier studies showed that inbred mouse strains had different susceptibility to cerulein-induced pancreatitis. Here, we confirm and extend these findings by characterizing the severity of acute and recurrent acute pancreatitis in the C57BL/6N and FVB/N strains. When acute pancreatitis was induced with repeated cerulein injections, FVB/N mice had more severe pancreatic edema, higher plasma amylase levels, increased inflammatory cell infiltration, and more extensive acinar cell necrosis relative to the C57BL/6N strain. Cerulein elicited higher and more sustained trypsin activity in FVB/N mice relative to C57BL/6N animals, which was likely due to the lower expression of the SPINK1 trypsin inhibitor and the trypsinogen-degrading lysosomal protease cathepsin L. In C57BL/6N mice, we previously showed that pancreatitis responses were more severe during a second attack compared with the initial, sentinel episode. In FVB/N mice, we now found that the second episode was associated with lower pancreas edema and plasma amylase but higher inflammatory cell infiltration than the first attack. The observations reinforce the notion that inbred mouse strains exhibit differences in their pathological responses during acute and recurrent acute pancreatitis.
使用促分泌素雨蛙肽进行过度刺激是研究小鼠急性、复发性急性和慢性胰腺炎常用的实验模型。早期研究表明，近交系小鼠品系对雨蛙肽诱导的胰腺炎易感性不同。在此，我们通过描述C57BL/6N和FVB/N品系急性和复发性急性胰腺炎的严重程度来证实并扩展这些发现。当用重复注射雨蛙肽诱导急性胰腺炎时，相对于C57BL/6N品系，FVB/N小鼠有更严重的胰腺水肿、更高的血浆淀粉酶水平、增加的炎性细胞浸润以及更广泛的腺泡细胞坏死。相对于C57BL/ animals，雨蛙肽在FVB/N小鼠中引发更高且更持久的胰蛋白酶活性，这可能是由于丝氨酸蛋白酶抑制剂Kazal型1（SPINK1）和降解胰蛋白酶原的溶酶体蛋白酶组织蛋白酶L的表达较低。在C57BL/6N小鼠中，我们之前表明与初始的哨兵发作相比，第二次发作时胰腺炎反应更严重。在FVB/N小鼠中，我们现在发现第二次发作与第一次发作相比，胰腺水肿和血浆淀粉酶较低，但炎性细胞浸润较高。这些观察结果强化了这样一种观念，即近交系小鼠品系在急性和复发性急性胰腺炎期间的病理反应存在差异。
