3.1　Features of Chronic Pancreatitis

Both morphological changes and clinical symptoms characterize chronic pancreatitis and their knowledge is of importance for a comprehensive understanding of the available experimental models with their strengths and limitations.So far there is no animal model that incorporates all features of chronic pancreatitis that are seen in humans.Secondly，a variety of animal models exist that，although mimicking chronic pancreatitis，differ among each other regarding their morphologic and clinical characteristics.Choosing the right models is of importance and depends on the scientific question that is addressed by the investigator.

From a histopathologic point of view chronic pancreatitis is a progressive and destructive inflammatory process of the pancreatic parenchyma that finally involves ductal changes as well.In some cases the kind of histologic damage allows a deduction of the etiology of chronic pancreatitis，as some causative factors show typical histologic features（Klöppel 2013；Kloppel et al.2004）.Generally chronic pancreatitis starts with focal necrosis and inflammatory cell invasion.When pancreatic stellate cells are activated collagen deposition occurs leading to fibrosis of the organ.In early stages and particularly in alcoholic chronic pancreatitis fibrosis is mainly localized in a perilobular pattern that later affects the parenchyma（intralobular fibrosis）（Klöppel 2013）.In late stages ductal changes with irregularities of the lumen width and strictures are seen that are the result of tissue traction due to fibrosis and scarring.Ductal changes ultimately predispose to precipitation of calculi and protein plugs（Ammann et al.1996；Detlefsen et al.2006；Kloppel 2007）.(https://www.daowen.com)

Typical clinical manifestations are pancreatic pain，steatorrhoea with weight loss and maldigestion due to exocrine insufficiency and impaired glucose tolerance up to manifest diabetes mellitus（Muniraj et al.2014；Schütte et al.2013）.Continuous maldigestion without medical intervention leads to malnutrition with additional complications such as osteoporosis and vitamin deficiency（Gupte and Forsmark 2014）.Signs of exocrine insufficiency occur late when secretory function is reduced to less than 10%of normal（Keller et al.2009）.