Establishment of animal models for three types of pancreatitis and analyses of regeneration mechanisms.
OBJECTIVE
To investigate the mechanisms underlying the onset and progress of pancreatitis, 3 animal models (chronic, acute, and severe pancreatitis) were established by double ligature of the pancreatic duct, injection with cerulein, or injection with cerulein + double ligature of the pancreatic duct.


METHODS
We prepared a control and 3 experimental groups: group 1 (untreated control), group 2 (a chronic pancreatitis model; the pancreatic tail was exposed through a midline incision, and the pancreatic duct from this part was double-ligated), group 3 (an acute pancreatitis model; cerulein was intraperitoneally injected 7 times on day 0), and group 4 (a severe pancreatitis model; the double ligature of the pancreatic duct plus injection of cerulein).


RESULTS
Kinetic observations of survival rate, relative pancreatic weight, and the macroscopical and microscopical diagnoses and observations of the changes in endocrine function clearly show that these 3 murine models of pancreatitis can serve as human models for chronic, acute, and severe pancreatitis. Furthermore, pancreas duodenum homeobox 1, cytokeratin 19, and Ki67 are expressed at the site of injury in the pancreas, resulting from the injection with cerulein and/or double ligature of the pancreatic ducts and indicating that there remains a tissue-regenerative capacity.


CONCLUSIONS
These 3 mouse models could serve as human models for chronic, acute, and severe pancreatitis. Furthermore, cells of the epithelial lineage might participate in tissue regeneration in chronic, acute, and severe pancreatitis.
Sakaguchi
Yutaku
Y
First Department of Pathology, Kansai Medical University, Moriguchi City, Osaka, Japan.
Inaba
Muneo
M
Kusafuka
Kimihide
K
Okazaki
Kazuichi
K
Ikehara
Susumu
S
D000681:Amylases / Q000097:blood; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D049109:Cell Proliferation; D002108:Ceruletide; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D018398:Homeodomain Proteins / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000378:metabolism; D053539:Keratin-19 / Q000378:metabolism; D008026:Ligation; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D010179:Pancreas / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010183:Pancreatic Ducts / Q000601:surgery; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D050500:Pancreatitis, Chronic / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D012038:Regeneration; D012720:Severity of Illness Index; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism
D015415:Biomarkers; D001786:Blood Glucose; D018398:Homeodomain Proteins; D007328:Insulin; D053539:Keratin-19; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D002108:Ceruletide; D000681:Amylases