Schmeling D J, Oldham K T, Guice K S, Kunkel R G, Johnson K J
Department of Surgery, University of Michigan Medical School, Ann Arbor.
Ann Surg. 1991 Apr;213(4):350-5. doi: 10.1097/00000658-199104000-00010.
Noninfectious obliterative cholangitis results from biliary tract inflammation in clinical conditions such as biliary atresia and sclerosing cholangitis. The purpose of this study was to develop an animal model of noninfectious biliary tract inflammation and fibrosis. An implantable osmotic pump was connected to a catheter placed into the gallbladder of hamsters. Phorbol myristate acetate (PMA) was infused into the biliary tract for periods of 6 hours to 28 days. After 7 days the animals developed neutrophil infiltration, cellular necrosis, and edema of the biliary ducts. After 14 days, the animals demonstrated intrahepatic cholestasis with bile duct fibrosis and acute and chronic inflammatory cell infiltration. By 28 days pronounced portal fibrosis was present, some of which created an early bridging cirrhosis pattern. In addition there was evidence of neocholangiogenesis. We conclude that long-term PMA infusion into the biliary tract generates an inflammatory response characterized by obliterative cholangitis and fibrosis, sharing many of the histologic features of human biliary atresia. This model may provide a relatively simple technique for investigating the process of nonpyogenic biliary tract inflammation.
非感染性闭塞性胆管炎源于诸如胆道闭锁和硬化性胆管炎等临床病症中的胆道炎症。本研究的目的是建立一种非感染性胆道炎症和纤维化的动物模型。将一个可植入式渗透泵连接到置于仓鼠胆囊内的导管上。将佛波酯（PMA）注入胆道，持续6小时至28天。7天后，动物出现中性粒细胞浸润、细胞坏死和胆管水肿。14天后，动物表现出肝内胆汁淤积，伴有胆管纤维化以及急性和慢性炎性细胞浸润。到28天时，出现明显的门脉纤维化，其中一些形成了早期桥接性肝硬化模式。此外，有新胆管生成的证据。我们得出结论，长期向胆道内注入PMA会引发以闭塞性胆管炎和纤维化为特征的炎症反应，具有许多人类胆道闭锁的组织学特征。该模型可能为研究非化脓性胆道炎症过程提供一种相对简单的技术。
