【摘要】 目的　了解轮状病毒致新生鼠胆管损伤的分子机制。方法　实验共需成年雄性鼠 13只 ,雌性鼠 2 5只。将小鼠按每笼 1只雄性与 2只雌性的比例将动物分成 13笼 ,饲养于层流室内 ,新生鼠出生后 2 4～ 4 8h内将其随机分成 5组 ,每组 5窝 ,每窝 5～ 8只。不同组腹腔内注射不同滴度的猴轮状病毒MMU180 0 6 ,其中一组加用吡咯二硫氨基甲酯 (PDTC) ,对照组腹腔注射相同剂量的病毒培养液。在注射病毒后 5、10、15、2 1及 2 8d各处死一批动物 ,观察动物的体重变化及肝内外胆管的组织学改变。免疫组化法检测轮状病毒VP7抗原及NF κB在肝内外胆管中的表达 ,并对NF κB的表达进行原位杂交研究。结果　病毒注射组小鼠体重的增加明显慢于对照组。病毒注射后鼠肝胆系统出现急慢性炎症反应 ,且可见肝外胆管狭窄及胆道闭锁。病毒注射组均可检测到病毒抗原。病毒注射后NF κB的表达在蛋白质水平与mRNA水平均增高 ,PDTC能抑制NF κB的表达增高并可减轻炎症反应的程度。结论　NF κB在介导轮状病毒对新生鼠肝内外胆管损伤中有重要作用 ,这种作用可被PDTC所抑制。更多还原

【Abstract】 Objective To investigate the mechanism of rotavirus induced biliary tract damage in BALB/C mice.Methods Neonate mice received intraperitoneal injection of 1) rotavirus; 2) rotavirus plus PDTC and 3) culture medium only (control group) respectively between 24 to 48 hours of life. The intra and extrahepatic bile ducts were dissected out after 5, 10, 15, 21 and 28 days. The mice gain weight and histopathological patterns of the intra and extrahepatic bile ducts were recorded. Rotavirus was immunostained with VP 7 antigen. The expressions of nuclear factor κB both in the intra- and extrahepatic bile ducts were also shown with immuno histochemical staining and in situ hybridization.Results The gain weight of the infected mice was slower than that of control group. Acute and chronic inflammation of the intra and extrahepatic bile ducts and the stenosis of extrahepatic bile ducts could be detected in the infected mice. Extrahepatic bile ducts atresia was detected in mice inoculated with 10 7 plaque forming unite of rotavirus. The expression of VP7 of rotavirus could be detected in the liver and extrahepatic bile ducts. The expression of nuclear factor κB both in the intra and extrahepatic bile ducts was increased in all infected groups. But the damage of bile ducts was mitigated after injection of PDTC.Conclusion The extrahepatic biliary atresia in BALB/C mice induced by rotavirus is mediated by nuclear factor κB.更多还原