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New strategy for the treatment of sudden-onset hearing loss based on ischemic cell damage theory

基于缺血细胞损伤理论治疗突发性耳聋的新策略

基本信息

批准号：
16390489
负责人：
GYO Kiyofumi
金额：
$ 9.15万
依托单位：
Ehime University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

Underlining mechanisms of an ischemic cochlear damage were investigated using Mongolian gerbils. The animals were subjected to ischemic insult by occluding the vertebral arteries bilaterally for 15 min. The ischemia caused severer damage at the basal turn than at the apical turn. At the spiral ganglion, the number of neurons decreased gradually by ischemic insult ; to be 71% of preischemic level at day 7. Bax, an apoptosis-related protein, was noted prominently at day 1, which gradually disappeared thereafter. At the stria vascularis, positive immunostaining for connexin 26 decreased on day 1, but recovered to some extent at day 4 and completely healed at day 7. At the organ of Corti, the auditory hair cells were sporadically damaged due to apoptotic process, more prominently in the inner hair cells. From a study with glutamate transporter knock-out mice, glutamate was proved to be a key substance in aggravating the ischemic cochlear damage.Three treatment modalities were assessed in this study. 1.Ginsenoside Rb1, which belongs to Kanpo medicine, was proved effective in prevention of ischemic cochlear damage. 2.Prosaposin, which is know to have neurotrophic effects, was also effective in protecting the ischemic cochlear damage. Stem cells derived from bone marrow prevented ischemic damage of the hair cells and the spiral ganglion cells, probably via release of neurotrophic factors. However, they were not effective in facilitating regeneration of the hair cells.

用蒙古沙土鼠研究了缺血性耳蜗损伤的机制。动物进行缺血性损伤，闭塞双侧椎动脉15分钟。缺血引起的损伤比在顶端转向在基底转向。在螺旋神经节，神经元的数量逐渐减少缺血性损伤，是71%的缺血前水平在第7天。Bax是一种凋亡相关蛋白，在第1天显著表达，此后逐渐消失。在血管纹，阳性免疫染色连接蛋白26下降的第1天，但在一定程度上恢复在第4天，并在第7天完全愈合。在Corti器，由于凋亡过程，听毛细胞零星受损，在内毛细胞中更为突出。谷氨酸转运蛋白基因敲除小鼠实验证实谷氨酸是加重缺血性耳蜗损伤的关键物质。1.人参皂苷Rb_1属于坎珀类药物，对缺血性耳蜗损伤有明显的预防作用。2.具有神经营养作用的Prosaposin对缺血性耳蜗损伤也有保护作用。来自骨髓的干细胞可能通过释放神经营养因子来防止毛细胞和螺旋神经节细胞的缺血性损伤。然而，它们不能有效促进毛细胞的再生。