目的:通过模拟人巨细胞病毒(HCMV)宫内传播建立小鼠巨细胞病毒(MCMV)宫内感染模型,研究胎鼠感染后脑的病理学变化。方法:用ELISA方法筛选无MCMV感染史的SPF级BALB1c雌雄小鼠32只,同笼受孕后,感染组在小鼠孕龄12.5天时通过胎盘显微接种MCMV悬液,对照组则接种等体积的3%FCS DMEM,待孕龄18.5天时剖腹取出49份胎鼠脑组织,用光镜和透射电射观察神经元的显微和超微结构,并进行病毒分离及PCR检测胎盘和胎脑感染情况。结果:光镜下可见感染组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MCMV特征性嗜酸性包涵体;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,病毒分离阳性。在同时设置对照组则无上述阳性发现。结论:MCMV能通过小鼠胎盘感染胎鼠脑组织,并导致神经元结构破坏。该实验为探讨先天性HCMV脑炎的发病机理提供有力的工具。
Objective: To research brain pathological change of fetal mice based on intrauterine infection model of murine cytomegalovirus by simulating intrauterine transmission of cytomegalovirus. Methods: ELISA was used to screen 32 SPF BALB1 c mice without infection history of cytomegalovirus,after caging for mating,the mice in infection group were inoculated with cytomegalovirus suspension at12. 5 days during pregnancy,while the mice in control group were inoculated with 3%FCS DMEM of the same volume; 49 brain tissue specimens of fetal mice were obtained at 18. 5 days during pregnancy; light microscope and electron microscope were used to observe microstructure and ultramicrostructure; placental infection and fetal brain infection situations were detected after virus isolation and PCR. Results: The pathological changes under light microscope consisted of brain capillary vasodilatation and congestion,obvious decrease of number of neurons,ischemic changes of the remaining neurons,interstitial edema,softening focus,and cytomegalovirus acidophilous inclusion bodies in cell nuclei and cytoplasma of infected neurons; the pathological changes under electron microscope consisted of disappearance of infected neurons,heavy damages( liking physalides or lysis) of important organelles( mitochondria,endoplasmic reticulum,and Golgi complex),virus isolation was positive. In control group,no above-mentioned positive change was found. Conclusion: Cytomegalovirus can damage neurons by infecting fetal brain via placenta; the study provides a basis for researching the pathogenesis of congenital encephalitis induced by cytomegalovirus.