Animal models for investigating chronic pancreatitis

Abstract

Chronic pancreatitis is defined as a continuous or recurrent inflammatory disease of the pancreas characterized by progressive and irreversible morphological changes. It typically causes pain and permanent impairment of pancreatic function. In chronic pancreatitis areas of focal necrosis are followed by perilobular and intralobular fibrosis of the parenchyma, by stone formation in the pancreatic duct, calcifications in the parenchyma as well as the formation of pseudocysts. Late in the course of the disease a progressive loss of endocrine and exocrine function occurs. Despite advances in understanding the pathogenesis no causal treatment for chronic pancreatitis is presently available. Thus, there is a need for well characterized animal models for further investigations that allow translation to the human situation. This review summarizes existing experimental models and distinguishes them according to the type of pathological stimulus used for induction of pancreatitis. There is a special focus on pancreatic duct ligation, repetitive overstimulation with caerulein and chronic alcohol feeding. Secondly, attention is drawn to genetic models that have recently been generated and which mimic features of chronic pancreatitis in man. Each technique will be supplemented with data on the pathophysiological background of the model and their limitations will be discussed.

Long-term evolution of acinar-to-ductal metaplasia and β-cell mass after radiofrequency-assisted transection of the pancreas in a controlled large animal model

“…Ever since the first studies on PDL in mouse models it has been said that this technique is difficult because its unique anatomy hampers the results [15,16]. The mouse pancreas is usually poorly defined and consists of three lobes (gastric, splenic and duodenal) which drain their juices via individual ducts only 150 µm in diameter [16,17] and there are also frequent variations in this drainage. Researchers usually ligate the splenic lobe from the rest of the pancreas, however this technique is challenging due to the small diameter of the pancreatic duct and usually requires the help of a microscope for the dissection.…”

Composition of Gastric Juice and Bile in Rats at the Experimental Chronic Pancreatitis

“…В результаті порушення кровоо-бігу, гіпоксії та морфологічних змін стражда-ють жовчоутворювальна, білоксинтезувальна, детоксикаційна та інші функції печінки, що в свою чергу погіршує перебіг панкреатиту [5,8,9]. Зважаючи на актуальність вивчення ме-ханізмів формування та перебігу гострого і хронічного панкреатитів, а також особливо-стей функціонування інших органів і систем при цих патологіях, різними авторами було запропоновано низку інвазивних та неінва-зивних експериментальних моделей панкре-атитів [7,10]. Однією з неінвазивних та легко відтворюваних моделей як гострого, так і хронічного панкреатиту є L-аргінінова, при якій не пошкоджуються острівці Лангерган-са, тобто не страждає ендокринна функція підшлункової залози [11].…”

The triterpenoid CDDO-imidazolide reduces immune cell infiltration and cytokine secretion in the KrasG12D;Pdx1-Cre (KC) mouse model of pancreatic cancer

“…once a week for 4 weeks (11), lipopolysaccharide (LPS) induces chronic inflammation and early pancreatic lesions in mice with an activating Kras mutation in pancreatic acinar cells. LPS is not routinely used to induce pancreatitis (14) in animal models, even though it is widely used to trigger an inflammatory response, including the release of inflammatory cytokines from macrophages, both in vitro and in vivo. The effects of LPSinduced inflammation on immune cell infiltration and cytokine secretion in KC mice are not known.…”