Polycystic kidney rat is a novel animal model of Caroli's disease associated with congenital hepatic fibrosis
Polycystic kidney rat is a novel animal model of Caroli's disease associated with congenital hepatic fibrosis
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DOI：
10.1016/s0002-9440(10)64116-8
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发表时间：
2001-05-01
影响因子：
6
通讯作者：
Nakanuma, Y
中科院分区：
文献类型：
--
作者：
Sanzen, T;Harada, K;Nakanuma, Y
Caroli病（先天性肝内胆管扩张）与先天性肝纤维化相关，是一种常染色体隐性遗传性多囊肾病。最近，多囊肾（PCK）大鼠，一个自发的突变来自一个群体的Crj：CD大鼠与多囊性病变的肝脏和常染色体隐性遗传方式，报道。在本研究中，评价了PCK大鼠胎仔（妊娠第18 - 21天）、新生儿和成年大鼠（分娩后1 - 4个月）的肝胆系统病理学和胆汁细胞动力学。Crj：CD大鼠作为对照。在妊娠19天的胎儿中首次观察到肝内胆管的多节段性和囊状扩张。扩张扩散到整个肝脏，扩张程度随着年龄的增长而增加。胆管板畸形的大体和组织学特征在肝内胆管中很常见。门静脉结缔组织过度生长是明显的，并在分娩后进行。这些特征与先天性肝纤维化的Caroli病非常相似。在发育过程中，PCK大鼠的胆管上皮细胞的增殖活性大于对照组。与此相反，胆管上皮细胞凋亡是不广泛的PCK大鼠比对照组，直到1周后交付，但3周后更大，这表明在未成熟的胆管重塑缺陷与细胞动力学的不平衡发挥了作用，在PCK大鼠肝内胆管异常的发生。PCK大鼠是一种有前途的Caroli病伴先天性肝纤维化动物模型。
Caroli's disease (congenital intrahepatic biliary dilatation) associated with congenital hepatic fibrosis is an autosomal recessive polycystic kidney disease. Recently, the polycystic kidney (PCK) rat, a spontaneous mutant derived from a colony of Crj:CD rats with polycystic lesions in the liver and an autosomal recessive mode of inheritance, was reported. In the present study, the pathology of the hepatobiliary system and the biliary cell-kinetics were evaluated in fetuses (day 18 to 21 of gestation) and neonates and adults (1 day to 4 months after delivery) of PCK rats. Crj:CD rats were used as a control. Multiple segmental and saccular dilatations of intrahepatic bile ducts were first observed in fetuses at 19 days of gestation. The dilatation spread throughout the liver and the degree of dilatation increased with aging. Gross and histological features characterizing ductal plate malformation were common in the intrahepatic bile ducts. Overgrowth of portal connective tissue was evident and progressive after delivery. These features were very similar to those of Caroli's disease with congenital hepatic fibrosis. Proliferative activity in the biliary epithelial cells was greater in PCK rats than controls during the development. In contrast, the biliary epithelial apoptosis was less extensive in PCK rats than the controls until 1 week after delivery, but greater after 3 weeks, suggesting that the remodeling defect in immature bile ducts associated with the imbalance of cell kinetics plays a role in the occurrence of intrahepatic biliary anomalies in PCK rats. The PCK rat could be a useful and promising animal model of Caroli's disease with congenital hepatic fibrosis.