Acute pancreatitis (AP) is a common acute abdominal condition in clinical practice, with complex etiology and a mortality rate of 5% to 10%. The mortality rate for severe AP can reach 20% to 30%. The pathogenesis is not yet fully understood, and there are no specific treatment methods. Current methods for creating live AP animal models include pancreatic duct ligation, duodenal loop closure, pancreatic bile duct puncture injection, subcapsular pancreatic injection, pancreaticobiliary injection combined with intravenous infusion, and intraperitoneal injection of caerulein combined with lipopolysaccharide.
Caerulein is a gastric regulatory molecule that is functionally and compositionally similar to cholecystokinin (CCK). It stimulates excessive secretion of pancreatic acinar cells, causing a separation disorder of intracellular trypsinogen and lysosomal hydrolases. Activation occurs in a cathepsin B-dependent manner, and the activity of pancreatic enzymes can further lead to proenzyme activation, causing a series of protease activities that lead to cellular damage. The inflammatory response caused by self-digestion of pancreatic tissue recruits inflammatory cells and releases inflammatory factors, which can further cause severe local or even systemic inflammatory responses.
Figure 1. Caerulein chemical structure (CAS NO.17650-98-5)
This model has been successfully applied in rats, mice, dogs and Syrian hamsters etc, and is suitable for studying impaired autophagy, pathological calcium signaling, and ER stress, in which AP is characterised by variation in the amount of caerulein, by adjusting the number of injections, resulting in differences in degree of severity.
Protocol of Caerulein induced AP model
Preparation of cerulein solution
Dissolve 1 mg of caerulein in 1 mL of saline. Sterilize with 0.22 μm membrane filter and store at -20°C. Thaw before use and dilute with saline to 5 μg/mL or 10 μg/mL working solution.
Animal Preparation
Caerulein can induce AP in most animals, mainly used in rodents (such as rats and mice).
Drug administration
The AP induced by caerulein is mostly oedematous type, which is mostly used in the study of mild AP (MAP) and the conversion of MAP to SAP. For SAP research, caerulein is often combined with other compounds to achieve increased severity of AP, for example, lipopolysaccharide (LPS).
Animals were fasted but could drink freely 12 hours before surgery. Intraperitoneal injection with Caerulein (20-100 μg/kg, usually 50 μg/kg) every hour for 7 h, followed by one injection of 10 mg/kg LPS.
Model evaluation
1）Serum amylase and lipase activities increased.
2）Elevated NO concentration in serum.
3）Pancreatic pathology: pancreatic tissue edema with vacuoles, inflammatory cell infiltration, periductal and focal acinar cell necrosis.
4） Increased expression of inflammatory factors in serum and pancreatic tissue.
Model advantages
The method is simple, easy to copy, good repeatability, non-invasive.
Application case(Cat#60321ES Caerulein)
Figure 2. AP model related results in Balb / c mice (PMID: 35339899, IF: 5.736)
Balb/c mice were intraperitoneally injected with 50 μg/kg caerulein (Yeasen, Cat#60321ES) seven times at 1-hour intervals, and LPS (10 mg/kg) was administered simultaneously with the last dose to induce SAP. Pancreatic H&E images and histological scoring (b), as well as serum levels of amylase (c), IL-6 (d), and ALT (e) were evaluated.
Figure 3. Results of AP model correlation in Kunming mice (PMID: 27579473, IF: 4.096)
Female Kunming mice were intraperitoneally injected with 50 μg/kg caerulein (Yeasen, Cat#60321ES) four times at 1-hour intervals to induce AP. Levels of amylase, lipase, and TNFα in the serum (A), and pancreatic H&E images and histological scoring (C) were assessed.
Ordering Information
|
Product Name |
Cat# |
Specification |
|
Caerulein |
60321ES03 |
1 mg |
|
LPS,from Escherichia coli O55:B5 |
60747ES08/10 |
5 mg/10 mg |
|
LPS,from Escherichia coli O111:B4 |
60748ES08/10 |
5 mg/10 mg |