Comparable Responses in Male and Female Mice to Cerulein-Induced Chronic Pancreatic Injury and Recovery

Objective The cerulein-induced mouse pancreatitis model is a well-established, commonly used representation of human chronic pancreatitis pathology. Although studies report sex-dependent differences in human chronic pancreatitis, there are no studies in this model directly comparing sex response to pancreatic injury and recovery. Therefore, we designed a study to investigate whether sexdependent differences in chronic pancreatitis injury and recovery exist in the cerulein-induced pancreatitis model. Methods Adult male and female C57BL/6 mice were administered cerulein (50 μg/kg, 5 hourly intraperitoneal injections/day, 3 days/week) for 4 weeks to induce chronic pancreatitis; control mice received normal saline injections. Pancreata and blood were harvested at 4 days (as injury group) or 4 weeks (as recovery group) after the last injection. Amylase secretion was measured from the serum. Acinar injury was scored on H&E sections. Fibrosis was assessed by Sirius Red and collagen immunofluorescence staining. Results Compared to time-matched controls, injury group displayed decreased body and pancreas weight, and increased acinar injury and fibrosis, with no significant differences between males and females. Recovery group demonstrated recovery of body weight, partial recovery of pancreas weight, reversal of acinar injury, and partial reversal of fibrosis, with no significant differences between males and females. Amylase secretion/body weight was similar across all groups. Conclusions Male and female mice of the cerulein-induced chronic pancreatitis demonstrate similar responses to chronic pancreatitis injury and recovery. Although this model may not sufficiently emulate sex-dependent responses in human chronic pancreatitis, our study supports that both sexes of mice from this model can be used for the study of chronic pancreatitis.

Author(s): Tolulope F Obafemi, Peter Yu, Jing Li, Joy M Davis, Ka Liu, Binglu Cheng, Xiurong Zhao, Qiang Shen, Mamoun Younes, Tien C Ko, Yanna Cao

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