抄録
Complications such as malnutrition and diabetes often result from dysfunctional pancreatic endocrine and exocrine systems in pancreatitis. These systems also differ functionally during healing following pancreatitis. This study examined pancreatic regeneration in both patients with autoimmune pancreatitis (AIP) during treatment with prednisolone, and in two different rat models of acute pancreatitis. Human pancreatic tissue from AIP patients was immunostained to identify pancreatic cells in the phase of regeneration by using an anti-Ki-67 (a proliferation marker) antibody. One rat model used caerulein (CAE) to generate acute edematous pancreatitis (AEP), and the second involved administration of DL-ethionine to generate acute necrotizing pancreatitis (ANP) . A labeling index (LI) was established as the ratio of proliferating cell nuclear antigen (PCNA) -labeled acinar cells to total acinar cells, while the ratio of acinar cells showing mitosis to the total number of acinar cells was calculated as the mitotic index (MI) . Pancreatic progenitor cells were identified using an anti-pancreatic/duodenal homeobox-1 (PDX-1; an transcription activator) antibody. Additionally, anti-hairy/enhancer-of-split homologue-1 (HES-1) antibody was used to detect immature pancreatic exocrine cells. Human pancreatic tissue with AIP was immunostained. Ki-67-positive cells coincided with acinar cells and ductal cells, and PDX-1-positive cells coincided with pancreatic ductal-type cells. Some α-amylase-positive cells and most insulin- and glucagon-positive cells were PDX-1-positive. The severity of AEP was evident 4-12h after initial injection of CAE in the first rat model. The PCNA LI gradually increased to a maximum at 120h, while the MI peaked at 96 h. In rats with ANP, necrosis and inflammation were prominent but diminished during healing, while the PCNA-LI increased to a peak at 12 days after initial injection of ET, and the MI maximum occurred at 10 days. PDX-1 was strongly expressed only in islet cells after AEP, while expression following ANP was intense in islet cells, several ductal-type cells, and a few acinar cells. Few HES-1-positive cells were observed among acinar or ductal cells. This study clarified the temporal nature of pancreatic regeneration in two rat models of acute pancreatitis. The results indicated that regeneration after AEP in rats might not involve pancreatic progenitor cells. However, regeneration after ANP in rats and AIP in humans involves pancreatic progenitor cells that probably derive from the dedifferentiation of acinar and ductal cells affected by inflammation.
