先天性人巨细胞病毒肝炎小鼠模型的建立

Development of a mouse model of congenital human cytomegalovirus hepatitis

目的探讨建立人巨细胞病毒(HCMV)先天性感染致新生鼠肝炎模型的可行性。方法将HCMV-AD169接种至10周龄Balb/c雌雄小鼠腹腔后,随机选择配对。待雌鼠分娩后取出新生鼠肝脏,进行病毒分离、病理学检测及原位分子杂交检测。结果病理学研究结果证实,HCMV感染的新生小鼠肝组织中见点、灶状坏死,并可见巨核细胞。坏死区炎细胞浸润。核内可见偏于一端的包涵体,使细胞呈"猫头鹰眼"样,汇管区可见炎细胞浸润。局部肝脏包膜增厚。原位杂交结果显示,病毒核酸存在于受感染肝细胞内。病毒分离结果证实在新生鼠肝组织上清液中可分离出HCMV。结论 HCMV能侵袭Balb/c小鼠,并通过胎盘感染其子代,引起肝炎。这种模拟人类先天性巨细胞病毒肝炎的小鼠模型的建立为该病动物实验研究提供了可能。

Objective To define that Human Cytomegalovirus（HCMV） can cross the placenta of the BALB/C mice and initiate congenital human cytomegalovirus hepatitis of the newborn mice.Methods HCMV-AD169 was injected into the intraperitoneum of mice when they were about 10weeks old.Then,these of mice were arranged for mating at random.After the neonatal mice were given birth,their livers were removed and were used for virus isolates,pathology testing and in situ hybridization.Results The results observed showed that pathological changes consisting of point or multifocal necrosis,megakaryocytes.Inflammatory cells infiltrated in the necrotic area.Inclusion body located on one end of the cell nucleus,which made the cell like an ＂owe eye＂.Histology revealed the portal area inflammation.some local envelope thickened.Meanwhile the presence of virus sequences was confirmed by in situ hybridization,however,nothing was found in the normal controls.HCMV had also been isolated from the tissue supernatant.Conclusion Our research suggested that congenital human cytomegalovirus hepatitis of a neonatal mouse may be a result of transplacental transmission of HCMV during maternal infection.The mouse model will allow the study of the development of therapeutic agents on the congenital human cytomegalovirus hepatitis.