Ninomiya Masashi, Ueno Yoshiyuki, Shimosegawa Tooru
Division of Gastroenterology, Department of Gastroenterology, Tohoku University Graduate School of Medicine, Seiryo, Aoba-ku, Sendai 980-8575, Japan.
Int J Hepatol. 2012;2012:649290. doi: 10.1155/2012/649290. Epub 2011 Aug 8.
Primary Biliary Cirrhosis (PBC) is considered an autoimmune disease characterized by immune-mediated destruction of the intrahepatic bile ducts and its characteristic serologic marker, the anti-mitochondrial antibody (AMA). Several factors were proposed to clarify the pathological and immunological mechanisms of PBC. Immunological reaction with a bacterial or a viral association was identified in the previous report, and it seems probable that PBC was thought to have such an etiology. The majority of patients with PBC was reported to have both RT-PCR and immunohistochemistry evidence of human betaretrovirus infection in lymph nodes or in 2008, the patient who developed PBC with high HIV viral load had an antiviral therapy and recovered. To understand the etiology of PBC associated with infection, several factors should be considered and especially animal models may be useful. In this paper, we introduce three typical animal models of PBC: the dominant-negative form of transforming growth factor-β receptor type II (dnTGFβRII) mouse, IL-2Rα(-/-) mouse and NOD.c3c4 mouse, are enumerated and described, and we discuss previous reports of viral infection associated with PBC and consider the etiology of PBC from our analysis of results in NOD.c3c4 mouse.
原发性胆汁性肝硬化（PBC）被认为是一种自身免疫性疾病，其特征是免疫介导的肝内胆管破坏以及其特征性血清学标志物抗线粒体抗体（AMA）。人们提出了几个因素来阐明PBC的病理和免疫机制。先前的报告中发现了与细菌或病毒相关的免疫反应，并且PBC似乎可能有这样的病因。据报道，大多数PBC患者在淋巴结中同时有逆转录聚合酶链反应（RT-PCR）和免疫组化证据表明存在人类β逆转录病毒感染，或者在2008年，一名患有高HIV病毒载量并发展为PBC的患者接受了抗病毒治疗并康复。为了了解与感染相关的PBC的病因，应考虑几个因素，特别是动物模型可能会有所帮助。在本文中，我们介绍了三种典型的PBC动物模型：列举并描述了II型转化生长因子-β受体的显性负性形式（dnTGFβRII）小鼠、IL-2Rα（-/-）小鼠和NOD.c3c4小鼠，并且我们讨论了先前关于与PBC相关的病毒感染的报告，并根据我们对NOD.c3c4小鼠结果的分析来考虑PBC的病因。
