人巨细胞病毒感染胎鼠大脑皮质神经元显微和超微结构观察

Histopathological and ultrastructural changes of the neurons of cerebral cortex in fetal mice infected with human cytomegalovirus

目的 :研究人巨细胞病毒 (HCMV)经小鼠胎盘垂直传播致胎鼠大脑皮质神经元病理改变的显微和超微结构特征。方法 :在 8～ 12周龄Balb/c雌雄小鼠腹腔内接种HCMV后 ,交配 ,待孕鼠临产时剖腹取出 10份胎鼠双侧大脑皮质 ,用光镜和透射电射观察了神经元的显微和超微结构 ,同时进行了病毒分离。结果 :光镜下可见胎鼠脑微血管扩张充血 ,神经元数目明显减少 ,残存的神经元缺血性改变 ,间质水肿 ;可见到软化灶及受染神经元核内及胞质内HCMV特征性嗜碱性和嗜酸性包涵体 ,电镜下可见受染神经元核仁消失 ,胞质内线粒体、内质网和高尔基复合体等重要细胞器结构严重破坏呈空泡状或溶解 ;并找到人类疱疹病毒样颗粒。病毒分离阳性。在同时设置的正常对照组则无上述阳性发现。结论 :HCMV能通过小鼠胎盘感染子代胎鼠大脑皮质神经元 。

Purpose To investigate the histopathological and ultrastructural changes of the neurons of fetal mice from the cerebral cortex with human cytomegalovirus infection. Methods HCMV AD169(5 0 log TCID50 in 0 5 ml/mouse)was injected into the intraperitoneum of mice(half of them were female) when they were about 8～12 weeks old. The mice were then arranged for mating. Pregnancies were dated as day 0 when a copulation plug was found. 10 of fetuses on the day about to be given birth of gestation were removed from the uteri and its cerebral cortex were removed from the skull. The histopathology and ultrastructrure of the neurons of its cerebral cortex were observed with light and electron microscopes. Meanwhile,the supernatant of minced fetal mouse brain tissue was used for virus isolates by HF cells. Results The pathological changes consisted of destructive meningoencephalitis and large, basophilic, intranuclear and acidophilous intracytoplasmic neuronal inclusions of viral type occurred in the fetal mouse brain. Part of the neurons were lost, and the remaining had the ischemia changes and oedema. Partial of the neurons with the nucleolus disappearance, nuclear and cytoplasma membrane breakage, mitochondrial enlarging, strong cytoplasm changes or flowing out were observed from different tissue sections of the infected cerebral cortex of fetal mice by transmission electron microscope. Meanwhile, HCMV had also been isolated from the supernatant of the fetal mice cerebral cortex, however, no pathological changes was found in the normal controls. Conclusions HCMV can cross the placenta of the Balb/c mice and initiate congenital infection of cerebral cortex in the developing fetus and it is suggested that necrosis is a major form of cell death.