Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Clin Res Hepatol Gastroenterol. 2011 Dec;35(12):792-804. doi: 10.1016/j.clinre.2011.04.014. Epub 2011 Jun 23.
Cholangiopathies such as primary sclerosing cholangitis (PSC) represent an important group of liver diseases of the intra- and extrahepatic bile ducts frequently causing end-stage liver disease with significant morbidity and mortality due to limited treatment options. The relatively low incidence of PSC and the difficult accessibility of the human bile duct system for longitudinal studies may represent some of the critical reasons for the lack of profound knowledge in regard to PSC pathophysiology. Therefore, there is an urgent need for reliable, well-defined and easily reproducible animal models to learn more about the pathophysiology of PSC and to test novel treatment modalities. In an ideal world, immunogenetically predisposed animals would develop fibrous-obliterative cholangitis of the intra- and extrahepatic bile ducts in association with inflammation of the gut (especially colitis) in a highly reproducible manner allowing to test new drugs. To date, however, no such animal model is available. We aimed to provide a systematic overview of current available rodent models for sclerosing cholangitis and biliary fibrosis and therefore critically analyzed the characteristics of models for chemically-induced cholangitis, knock-out mouse models with cholangitis, cholangitis induced by infectious agents, models of experimental biliary obstruction, models involving enteric bacterial cell-wall components or colitis, and models of primary biliary epithelial and endothelial cell injury.
原发性硬化性胆管炎（PSC）等胆管疾病是一组重要的肝内外胆管疾病，由于治疗选择有限，常导致终末期肝病，发病率和死亡率高。PSC 的发病率相对较低，且人类胆管系统难以进行纵向研究，这可能是导致对 PSC 病理生理学缺乏深入了解的一些关键原因。因此，迫切需要可靠、明确且易于复制的动物模型，以更多地了解 PSC 的病理生理学，并测试新的治疗方法。在理想情况下，免疫遗传易感性动物会以高度可重复的方式发生肝内外胆管纤维性闭塞性胆管炎，并伴有肠道炎症（尤其是结肠炎），从而能够测试新药。然而，到目前为止，还没有这样的动物模型。我们旨在提供当前用于硬化性胆管炎和胆汁性纤维化的啮齿动物模型的系统综述，因此对化学诱导性胆管炎模型、具有胆管炎的基因敲除小鼠模型、感染因子引起的胆管炎、实验性胆道梗阻模型、涉及肠细菌细胞壁成分或结肠炎的模型以及原发性胆汁性上皮和内皮细胞损伤的模型的特征进行了批判性分析。
