New aspects in a murine model for extrahepatic biliary atresia
New aspects in a murine model for extrahepatic biliary atresia
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DOI：
10.1016/s0022-3468(97)90680-1
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发表时间：
1997-08-01
影响因子：
2.4
通讯作者：
Mildenberger, H
中科院分区：
文献类型：
--
作者：
Petersen, C;Biermanns, D;Mildenberger, H
肝外胆道闭锁（EHBA）的病因尚不清楚，甚至缺乏动物模型。在鼠感染模型（感染恒河猴轮状病毒A组[RRV]的新生Balb/c小鼠）中的观察结果报告了与患有EHBA的儿童中的结果相似的肝外胆道梗阻。本研究重复上述动物实验，观察3周以上的临床和组织形态学变化。89只新生小鼠感染RRV，67%的小鼠出现胆汁淤积和生长迟缓的体征。其中8只动物自发恢复，而其他动物仍存在黄疸。间隔2天后，准备46只幼仔进行显微镜检查。从第5天开始，整个胆道出现水肿肿胀伴细胞浸润。10天后，在肝外胆管，发生了一个转变，其中向心性浸润导致完全阻塞，有时伴有狭窄前扩张。肝内病变表现为小胆管反应性坏死和增生。在一只19日龄小鼠中，观察到气球样扩张，类似于发育中的胆总管囊肿。RRV感染在新生Balb/c小鼠中诱导胆汁淤积的临床表现，不同病程的疾病主要导致完全性胆道梗阻和继发性肝脏变化，类似于儿童中的EHBA。这是第一个由感染引起的肝外胆管完全阻塞的EHBA动物模型。这些发现为进一步研究提供了新的基础。版权所有（C）1997 W.B.桑德斯公司
The cause of extrahepatic biliary atresia (EHBA) remains unknown, and even an animal model is still lacking. Observations in a murine infectious model (newborn Balb/c mice infected with rhesus rotavirus group A [RRV]) reported extrahepatic biliary obstruction similar to findings in children who have EHBA. In the present study, this animal experiment was repeated, and the clinical and histomorphologic changes were observed over 3 weeks. Eighty-nine newborn mice were infected with RRV, and 67% showed signs of cholestasis and delayed growth. Eight of these animals recovered spontaneously whereas the others remained icteric. Fourty-six pups were prepared for microscopic examination following a 2-day interval. From the fifth day, the whole biliary tract showed edematous swelling with cellular infiltration. Ten days later, in the extrahepatic bile duct, a transformation took place in which concentric infiltration led to complete obstruction, sometimes with prestenotic dilatation. The intrahepatic changes showed reactive necrosis and proliferation of the small bile ducts. In one 19-day-old mouse, a ballooning dilatation was observed, similar to a developing choledochal cyst. Infection with RRV induces in newborn Balb/c mice a cholestatic clinical picture with different courses of the disease leading mostly to complete biliary obstruction and secondary hepatic changes similar to EHBA in children. This is the first animal model for EHBA with complete obstruction of the extrahepatic bile duct induced by infection. These findings present a new basis for further studies. Copyright (C) 1997 by W.B. Saunders Company.