单纯疱疹病毒诱导NF-κB活化介导毛细胞病理性凋亡

The precise cause of sudden sensorineural hearing loss(SSNHL) has not been identified. Serological testing suggested that virus infection existed in a larger proportion of patients with SSNHL compared with normal controls. When certain infections were involved in the pathogenesis of SSNHL, the hearing was much worse in comparison to patients with no such indication of infection. Therefore, we put forth the hypothesis that SSNHL may be the result of pathologic activation of cellular stress pathways involving NF-κB within the cochlea. To validate the above hypothesis, Herpes Simplex Virus is inoculated into the middle ear of ICR mice, and the following tests are to be done 2h, 12h, 24h and 72h after virus inoculation: ①Concentrations of IL-1β、IL－6、TNF-α in perilymph ; ②The relationship between virus infection and NF-κB activation in hair cells, supporting cells , stria vascularis and spiral ganglions; ③BCL-2/BAX proteins changesand cell apoptosis in the cochlear ; ④ Auditory brainstem response audiometry of the mice. As controls, Pyrrolidine dithiocarbamate (PDTC),the special inhibitor of NF-κB, is subcutaneous injected before virus inoculation. And these tests are to be done again. Through the above experiments, we want to clarify the effect and its mechanism of NF-κB on the virus induced cell apoptosis, as well as put forward the mechanism of SSNHL.

突发性聋发病机制不明，鉴于血清学检查提示突发性聋患者病毒感染比例明显高于正常对照组，且潜在病毒感染致聋患者听力恢复较差，我们认为病毒感染致使毛细胞内NF-κB相关的细胞应激通路的病理性激活是突发性聋的病因之一。本研究拟于ICR小鼠鼓室内接种单纯疱疹病毒（HSV），于接种后2小时、12小时、24小时、72小时后，分别检测①外淋巴液IL-1β、IL－6、TNF-α含量改变；②毛细胞、支持细胞、血管纹、螺旋神经节等细胞病毒感染、NF-κB活化情况；③耳蜗组织 BCL-2/BAX蛋白表达与细胞凋亡情况；④小鼠听觉脑干诱发电位变化。另外，设立随机对照组，于病毒接种前皮下注射特异性NF-κB抑制剂毗咯烷二硫代氨基甲酸盐（PDTC），观察以上变化。以期阐明NF-κB在病毒感染诱发毛细胞凋亡中的作用及机制，为突发性聋的发病机制的阐明提供新思路。

突发性聋发病机制不明，我们认为病毒感染致使毛细胞内NF-κB相关的细胞应激通路的病理性激活是突发性聋的病因之一。本课题我们围绕以上假说，结合大样本的动物实验和临床研究，完成了以下内容：.1.单纯疱疹病毒小鼠鼓室内注射后可以引起毛细胞病理性凋亡，并造成不可逆性听力下降，NF-κB参与此病理过程。.2.收集了突发性聋患者的血清标本，检测其IL-1β/IL-6/TNF-a/IL-17a/TGF-β,发现其炎症介质水平明显高于正常人水平。说明炎症反应参与突发性聋的发生发展过程中。.3.收集罕见的突聋伴妊娠的患者，进行了鼓室内激素注射治疗，获得了良好的治疗效果。所有患者对鼓室内注射耐受良好，平均听力提高幅度为48±7.33dB，没有鼓膜穿孔或中耳感染等并发症。所有患者均分娩健康婴儿。