巨细胞病毒脑内感染小鼠听觉诱发电位的变化

目的 探讨脑内感染小鼠巨细胞病毒（murine cytomegalovirus,MCMV）后脑干听觉诱发电位（auditory brainstem response,ABR）的变化,以明确经脑内感染MCMV后小鼠ABR是否出现异常改变,从而验证经脑内感染MCMV能否建立巨细胞病毒（CMV）感染致听力损伤的动物模型,并在此基础上观察更昔洛韦对CMV感染致听力损伤的干预效果.方法 将24只新生小鼠按窝随机分成正常对照组、模型组、干预组3组,对照组经脑内注射无菌生理盐水10 μl,模型组与干预组经脑内接种TCID50为1×105 U/ml的MCMV病毒悬液10 μl,同时干预组在接种MCMV后第2天开始腹腔注射更昔洛韦60 mg/（kg·d）,连用2周.2周后在小鼠麻醉状态下应用脑干听觉诱发电位仪在电屏蔽装置中检测小鼠的ABR,并记录ABR的波形以及Ⅰ波的潜伏期、波幅.结果 模型组与正常对照组相比潜伏期延长、波幅降低（F=9.151,P=0.011;F=5.095,P=0.043）,更昔洛韦干预组与模型组相比潜伏期缩短、波幅升高（F=13.797,P=0.003;F=14.587,P=0.002）,差异有统计学意义.结论 经脑内感染MCMV可以引起小鼠ABR的异常改变,脑内感染MCMV可建立CMV感染致听力损伤的动物模型,婴幼儿CMV感染后早期应用更昔洛韦对CMV感染致听力损伤的进行性发展有一定的抑制作用.

A study of the changes in ABR following MCMV infection in mouse brain

Objective To investigate the changes in the auditory brainstem response （ABR） after the mice were infected by the murine cytomegalovirus （MCMV） in the brain so as to ascertain whether there is abnormality of the ABR, and to validate the establishment of animal model of the hearing loss caused by the CMV in mice with MCMV infection in the brain, based on which the effects of ganciclovir intervention on the hearing loss caused by MCMV was studied. Methods 24 newborn BALB/C mice were randomized into normal control group, model group and intervention group. The normal control group was injected with 10 μl of the sterile normal saline solution in the brain, the model group and intervention group were inoculated with 10 ill MCMV at 1 × 105U/ml as TCID50. The intervention group was peritoneally injected with ganciclovir （60 mg· kg^-1· d^-1 ） from the second day of MCMV inoculation and lasted 2 weeks. 2 week later, with the mice put under the ether anesthesia, an auditory evoked potential was used in electric shielding to detect the ABR and record the waveform of the ABR as well as the latency period and amplitude of wave I . Results The latency period of wave I in the model group was lengthened and the wave amplitude was reduced （ F = 9. 151, P = 0. 011 ; F = 5. 095, P = 0. 043 ） as compared with the normal control group ; In the ganciclovir intervention group, the latency period was reduced and wave amplitude the elevated （ F = 13. 797, P = 0. 003 ; F = 14. 587, P = 0. 002） as compared to the model group, and the differences were statistically significant. Conclusions The infection of the MCMV in the brain can lead to abnormal changes in the ABR in mice, and intracerebral infection of MCMV facilitates the establishment of animal model of hearing impairment caused by CMV infection. The application of gancielovir in the early phase of CMV infection in infants and young children has an inhibitory effort on the progressive aggravation of hearing impairment induced by CMV infection.