Huang Lei, Gu Wei-Zhong, Si Xin-Min, Wei Ming-Fa, Feng Jie-Xiong
Department of Pediatric Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
Hepatobiliary Pancreat Dis Int. 2007 Apr;6(2):188-93.
Biliary atresia, the etiology of which still remains unclear, occurs exclusively in newborns and most are infected with rotavirus. In this study, we aimed to investigate the histopathological patterns of different kinds of rotavirus in the liver and biliary tract of neonatal mice and the expression of NF-kappaB in the liver and biliary tract of infected mice.
Twenty-three adult mice (8 were male and 15 female) were divided into 8 breeding pairs, and each pair (1 male and 2 females) was housed in a cage in a laminar flow hood. Newborn mice, 24-48 hours old were randomly divided into A, B and C groups. The A and B groups were respectively inoculated with MMU18006 and SA11 rotavirus through the intraperitoneal route, while group C as blank control was only inoculated with culture medium. The liver was dissected after 5, 10, 15, 21 and 28 days; the weight of each mouse and the histopathological patterns in the liver were recorded. The expression of NF-kappaB in the liver and intrahepatic bile ducts was detected by immunohistochemical staining and the expression intensity was analyzed with a GT-2 imaging instrument.
The average increase in weight of infected mice was significantly slower than that of the normal control, while the growth rate of group A (injected with MMU18006 rotavirus) was slower than that of group B (SA11 rotavirus). In infected mice, the acute and chronic inflammation of liver and intra- and extra-hepatic bile ducts was more significant in group A. Stenosis was found in most intrahepatic bile ducts, and sporadically in extrahepatic bile ducts. The expression of NF-kappaB in infected mice was dramatically higher than that of the normal control, while the expression in group A was higher than in group B.
Significant damage to the liver and biliary tract of neonatal mice can be induced by inoculating MMU18006 rotavirus through the intraperitoneal route, which is very similar to the pathology of biliary atresia in the newborn human. Similar inoculation with SA11 rotavirus can only result in moderate impairment that disappears quickly. The difference of pathogenicity between the two rotaviruses may depend on their differing capacities to increase the expression of NF-kappaB in the liver and biliary tract.
胆道闭锁的病因仍不清楚，仅发生于新生儿，且大多数感染轮状病毒。在本研究中，我们旨在调查不同种类轮状病毒在新生小鼠肝脏和胆道中的组织病理学模式以及感染小鼠肝脏和胆道中核因子κB（NF-κB）的表达。
将23只成年小鼠（8只雄性，15只雌性）分成8对繁殖组，每对（1只雄性和2只雌性）饲养在层流柜中的一个笼子里。将24至48小时龄的新生小鼠随机分为A、B、C组。A组和B组分别通过腹腔途径接种MMU18006和SA11轮状病毒，而C组作为空白对照组仅接种培养基。在5、10、15、21和28天后解剖肝脏；记录每只小鼠的体重和肝脏中的组织病理学模式。通过免疫组织化学染色检测肝脏和肝内胆管中NF-κB的表达，并用GT-2成像仪分析表达强度。
感染小鼠的平均体重增加明显慢于正常对照组，而A组（注射MMU18006轮状病毒）的生长速度慢于B组（SA11轮状病毒）。在感染小鼠中，A组肝脏和肝内外胆管的急性和慢性炎症更明显。大多数肝内胆管发现狭窄，肝外胆管偶见狭窄。感染小鼠中NF-κB的表达明显高于正常对照组，而A组的表达高于B组。
通过腹腔途径接种MMU18006轮状病毒可诱导新生小鼠肝脏和胆道的显著损伤，这与人类新生儿胆道闭锁的病理学非常相似。类似地接种SA11轮状病毒只会导致中度损伤且很快消失。两种轮状病毒致病性的差异可能取决于它们在肝脏和胆道中增加NF-κB表达的不同能力。
