New Canine Model of Chronic Pancreatitis due to Chronic Ischemia with Incomplete Pancreatic Duct Obstruction

Tanaka, Tsuneo; Ichiba, Yasuyuki; Fujii, Yasufumi; Itoh, Hisao; Kodama, Osamu; Dohi, Kiyohiko

doi:10.1159/000199767

Cited by 23 publications

(13 citation statements)

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“…Complete PDL and partial PDL have been used for decades as models for acute and chronic pancreatitis in humans (9,10). Compared with complete PDL, the partial PDL model has several advantages.…”

Section: Discussionmentioning

confidence: 99%

“…Second, PDL induces robust pancreatitis through ductal occlusion, which may mimic the pathogenesis of pancreatitis in many humans. Third, acute pancreatitis by PDL progresses to chronic pancreatitis relatively quickly, which not only significantly shortens the experimental period but also allows easier detection of changes in the parameters of interest (9–11,41–43). …”

Section: Discussionmentioning

confidence: 99%

“…Among animal models for acute and chronic pancreatitis (8), partial pancreatic duct ligation (PDL) has been used to generate chronic pancreatitis in mammals (9,10). Ligation of the pancreatic duct immediately at the beginning of the splenic or tail part of the pancreas blocks the drainage of ductal fluid from the distal pancreas, resulting in autodigestion of acinar cells and severe inflammation specifically in the ligated tail of the pancreas, although initially the islets are largely unaffected.…”

Section: Introductionmentioning

confidence: 99%

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SMAD3/Stat3 Signaling Mediates β-Cell Epithelial-Mesenchymal Transition in Chronic Pancreatitis–Related Diabetes

et al. 2017

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Many patients with chronic pancreatitis develop diabetes (chronic pancreatitis–related diabetes [CPRD]) through an undetermined mechanism. Here we used long-term partial pancreatic duct ligation (PDL) as a model to study CPRD. We found that long-term PDL induced significant β-cell dedifferentiation, followed by a time-dependent decrease in functional β-cell mass—all specifically in the ligated tail portion of the pancreas (PDL-tail). High levels of transforming growth factor β1 (TGFβ1) were detected in the PDL-tail and were mainly produced by M2 macrophages at the early stage and by activated myofibroblasts at the later stage. Loss of β-cell mass was then found to result from TGFβ1-triggered epithelial-mesenchymal transition (EMT) by β-cells, rather than resulting directly from β-cell apoptosis. Mechanistically, TGFβ1-treated β-cells activated expression of the EMT regulator gene Snail in a SMAD3/Stat3-dependent manner. Moreover, forced expression of forkhead box protein O1 (FoxO1), an antagonist for activated Stat3, specifically in β-cells ameliorated β-cell EMT and β-cell loss and prevented the onset of diabetes in mice undergoing PDL. Together, our data suggest that chronic pancreatitis may trigger TGFβ1-mediated β-cell EMT to lead to CPRD, which could substantially be prevented by sustained expression of FoxO1 in β-cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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SMAD3/Stat3 Signaling Mediates β-Cell Epithelial-Mesenchymal Transition in Chronic Pancreatitis–Related Diabetes

et al. 2017

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“…Em cães, a ligadura de ramos da artéria esplênica contribui para a indução de pancreatite crônica 23 , mas protege o animal de infecção por pneumococo, quando associada à exérese do pólo inferior do baço 24 . A ligadura da artéria esplênica em coelhos diminui a resposta imune à administração intravenosa de antígenos morfologicamente modelados 25 .…”

Section: Introductionunclassified

Lípides plasmáticos em ratos após cirurgia esplênica - efeito de dois tipos de dieta

Paulo¹,

Paulo²,

Kalil³

et al. 2007

Rev. Assoc. Med. Bras.

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A esplenectomia total pode induzir complicações locais e sistêmicas 1 . Dessas, a mais temida é a infecção pós-esplenectomia 2,3 . As complicações infecciosas após a retirada do baço foram também descritas em animais de experimentação 4,5 . Além dessas complicações, têm sido relatadas, após esplenectomia, alterações no metabolismo lipídico, tanto em seres humanos 6-8 quanto em animais de experimentação [9][10][11][12][13] . Por essas razões, têm sido cada vez mais valorizadas as operações conservadoras sobre o baço. Nesse contexto, incluem-se as ligaduras vasculares. A ligadura da artéria esplênica é realizada como coadjuvante do tratamento do trauma esplênico 14,15 CONCLUSÃO. A esplenectomia total provoca aumento do colesterol total, da LDL-colesterol, da VLDL-colesterol e dos triglicérides, que é mais significante nos animais alimentados com a dieta acrescida de colesterol. A ligadura simultânea da artéria e da veia esplênicas previne contra as alterações dos níveis de lípides plasmáticos observadas em ratos submetidos à esplenectomia total e mantém esses níveis similares aos dos grupos controle e simulação.UNITERMOS: Baço / metabolismo. Esplenectomia / efeitos adversos. Esplenectomia / métodos. Ligadura da artéria esplênica. Ligadura da veia esplênica.quando associada à infusão de solução salina e comparada à esplenectomia 22 . Em cães, a ligadura de ramos da artéria esplênica contribui para a indução de pancreatite crônica 23, mas protege o animal de infecção por pneumococo, quando associada à exérese do pólo inferior do baço 24. A ligadura da artéria esplênica em coelhos diminui a resposta imune à administração intravenosa de antígenos morfologicamente modelados 25 . A ligadura simultânea da artéria e da veia esplênicas, com preservação do baço, em seres humanos, foi realizada na pancreatectomia caudal por laparatomia 26,27 e por via laparoscópica 28 . As conseqüências para o baço dessa ligadura simultânea foram recentemente descritas 29 . Não se sabe o efeito dessa ligadura nem de diferentes dietas sobre os níveis de lípides plasmáticos, em ratos. Por essas razões, planejamos estudar os efeitos da ligadura simultânea da artéria e veia esplênicas e da esplenectomia total sobre os níveis de lípides plasmáticos de ratos adultos, alimentados com dieta controle ou com dieta acrescida de 2,5% de colesterol.

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“…Earlier, we have reported that a combination of persistent paren chymal cell damage and pancreatic duct obstruction is important in producing a CP model (combination theory) [4], Clinically, various etiological factors including alco hol intake are recognized, but the pathophysiology of CP still remains obscure. Based on our investigations, we con sider ischemia as an important factor in the pathogenesis of CP [5], We reported the usefulness of our experimental CP model due to chronic ischemia with incomplete pan creatic duct obstruction [4], In this study, we investigated the change in exocrine pancreatic function and the histopathological findings in our model of CP due to chronic ischemia.…”

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confidence: 99%

Canine Model of Chronic Pancreatitis due to Chronic Ischemia

Tanaka¹,

Ichiba²,

Miura³

et al. 1994

Digestion

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An experimental model of chronic pancreatitis was produced by a chronic ischemia which was induced by ligation and separation of branches flowing into the left pancreatic lobe from the splenic artery. Macroscopic findings at 3 and 6 months after model preparation showed that the pancreas was hard, with severe inflammatory change. In the secretin-cerulein test at 3 and 6 months, the flow rate of pancreatic juice, amylase output and bicarbonate concentration were significantly reduced as compared with the controls. The histopathological findings consisted of a decrease in the pancreatic parenchyma, replacement of fat, severe inflammatory cell infiltration, extensive fibrosis and tubular complexes. As this model closely resembles human chronic pancreatitis, we conclude that ischemia is an etiological factor in chronic pancreatitis.

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New Canine Model of Chronic Pancreatitis due to Chronic Ischemia with Incomplete Pancreatic Duct Obstruction

Cited by 23 publications

References 5 publications

SMAD3/Stat3 Signaling Mediates β-Cell Epithelial-Mesenchymal Transition in Chronic Pancreatitis–Related Diabetes

SMAD3/Stat3 Signaling Mediates β-Cell Epithelial-Mesenchymal Transition in Chronic Pancreatitis–Related Diabetes

Lípides plasmáticos em ratos após cirurgia esplênica - efeito de dois tipos de dieta

Canine Model of Chronic Pancreatitis due to Chronic Ischemia

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