Medical University of Vienna, Institute of Pharmacology, Center for Physiology and Pharmacology, Vienna, Austria.
Expert Opin Drug Metab Toxicol. 2012 May;8(5):571-80. doi: 10.1517/17425255.2012.674511. Epub 2012 Mar 28.
Many different drugs and xenobiotics (chemical compounds foreign to an organism) can injure the bile duct epithelium and cause inflammatory bile duct diseases (cholangiopathies) ranging from transient cholestasis to vanishing bile duct syndrome, sclerosing cholangitis with development of biliary fibrosis and cirrhosis. Animal models of xenobiotic-induced liver injury have provided major mechanistic insights into the molecular mechanisms of xenobiotic-induced cholangiopathies and biliary fibrosis including primary biliary cirrhosis and primary sclerosing cholangitis.
In this review, the authors discuss the basic principles of xenobiotic-induced liver and bile duct injury and biliary fibrosis with emphasis on animal models. A PubMed search was performed using the search terms "xenobiotic," "liver injury," "cholestasis," and "biliary fibrosis." Reference lists of retrieved articles were also searched for relevant literature.
Xenobiotic-induced cholangiopathies are underestimated and frequently overlooked medical conditions due to their often transient nature. However, biliary disease may progress to vanishing bile duct syndrome, biliary fibrosis, and cirrhosis. Moreover, xenobiotics may prime the liver for subsequent liver disease by other agents and may also contribute to the development of hepatobiliary cancer though interaction with resident stem cells.
许多不同的药物和外源性化学物质（机体以外的化合物）可损伤胆管上皮，引起从短暂性胆汁淤积到消失性胆管综合征、伴有胆管纤维化和肝硬化的硬化性胆管炎等各种炎症性胆管疾病（胆管病）。外源性化学物质肝损伤的动物模型为外源性化学物质引起的胆管病和胆管纤维化（包括原发性胆汁性肝硬化和原发性硬化性胆管炎）的分子机制提供了主要的机制见解。
在这篇综述中，作者讨论了外源性化学物质引起的肝和胆管损伤及胆管纤维化的基本原理，重点介绍了动物模型。使用“外源性化学物质”、“肝损伤”、“胆汁淤积”和“胆管纤维化”等检索词在 PubMed 上进行了检索，并对检索到的文章的参考文献进行了搜索，以查找相关文献。
由于外源性化学物质引起的胆管病通常是短暂的，因此被低估且经常被忽视。然而，胆管疾病可能进展为消失性胆管综合征、胆管纤维化和肝硬化。此外，外源性化学物质可能通过与固有干细胞相互作用，通过其他制剂引发肝脏随后发生肝病，也可能促进肝胆癌的发生。
