Murine Models of Acute Pancreatitis: A Critical Appraisal of Clinical Relevance

Abstract

Acute pancreatitis (AP) is a severe disease associated with high morbidity and mortality. Clinical studies can provide some data concerning the etiology, pathophysiology, and outcomes of this disease. However, the study of early events and new targeted therapies cannot be performed on humans due to ethical reasons. Experimental murine models can be used in the understanding of the pancreatic inflammation, because they are able to closely mimic the main features of human AP, namely their histologic glandular changes and distant organ failure. These models continue to be important research tools for the reproduction of the etiological, environmental, and genetic factors associated with the pathogenesis of this inflammatory pathology and the exploration of novel therapeutic options. This review provides an overview of several murine models of AP. Furthermore, special focus is made on the most frequently carried out models, the protocols used, and their advantages and limitations. Finally, examples are provided of the use of these models to improve knowledge of the mechanisms involved in the pathogenesis, identify new biomarkers of severity, and develop new targeted therapies.

Keywords: acute pancreatitis; animal models; biomarkers; experimental models; inflammation; murine.

Figure 1

(A) Rat pancreas anatomy. Image: The pancreas of an adult rat showing the duodenum and common biliopancreatic duct. Rodent pancreas is soft and diffuse compared with the human pancreas. Photo provided by authors lab. a- duodenum; b- common biliopancreatic duct; c- pancreas. (B) Schematic showing the anatomy of rat pancreas. Image: picture showing the schematic anatomy of the pancreas, duodenum, and common biliopancreatic duct. a- duodenum; b- common biliopancreatic duct; c- pancreas.

Figure 2

Closed duodenal loop acute pancreatitis model. Image: picture showing the location of the closed loop of the duodenum. According to aseptic techniques, the duodenum is exposed by a laparotomy, the common biliopancreatic duct is identified, and the duodenum is obstructed by the placement of two ligatures: one just beyond the pylorus—that is, proximally to the duct—and the second placed distally to the duct (arrows).

Figure 3

Biliopancreatic duct injection acute pancreatitis model. Image: picture showing the retrograde ductal infusion technique. According to aseptic techniques, the duodenum is exposed by a laparotomy, and the common biliopancreatic duct is identified and cannulated; after the retrograde infusion, the duct is ligated (arrows).

Figure 4

Image: picture showing the site of ligation of the common biliopancreatic duct in the rat. According to aseptic techniques, the duodenum is exposed by a laparotomy; the common biliopancreatic duct is identified and ligated at the level of the duodenum (arrows).