Molecular biological investigation for the regeneration of inner ear sensory cells by controlling freeradical and apoptosis

通过控制自由基和细胞凋亡实现内耳感觉细胞再生的分子生物学研究

基本信息

批准号：
15390519
负责人：
TAKUMIDA Masaya
金额：
$ 4.42万
依托单位：
HIROSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

The aim of this study is to investigate the effects of free radicals (NO,ROS) and apoptosis to the inner ear disorders and to develop the new treatments for the inner ear disease by modulating and/or inhibiting the various steps of the mechanisms of inner ear disorders.As a result, certain stimuli induce the formation of free radicals, such as NO,ROS, resulting in a damage of inner ear. Subsequently, the sensory cells began to death by apoptosis. Calpain and caspase may play an important role for the apoptosis. These mechanisms were suggested to be a common pathway for almost all inner ear disorders. Based on these results, we investigated the attenuation of inner ear disorders by scavenging free radicals, inhibition of caspase or calpain and the addition of neurotrophines. All drugs used limited the hair cell damage and the combinations of drugs, such as inhibition of free radicals + neurotrophine, inhibition of free radicals + calpain or caspase inhibitors, had a significantly stronger preventive effect on hair cell damage. Based on these basic research, we have applied radical scavengers (rebamipide, vitamin C, glutathione) to the poor controlled Meniere's disease, cisplatin ototoxicity and presbyacusis. The results of these clinical trials are sufficient revealing an improvement of hearing.These results were presented at the meetings (13th and 14th meeting of the Otological Society of Japan, 62th and 63th meeting of Japan Society for Equilibrium Reseach, 40th Workshop on Inner Ear Biology) and were presented by 10 papers

这项研究的目的是研究自由基（NO，ROS）和凋亡对内耳疾病的影响，并通过调节和/或抑制内耳障碍机制的各种步骤来开发内耳疾病的新疗法。由于结果，某些刺激会诱导自由度，例如无自由基的损害，ros损坏了内在的内心损害内部。随后，感觉细胞开始因凋亡而死亡。钙蛋白酶和胱天蛋白酶对凋亡可能起重要作用。这些机制被认为是几乎所有内耳疾病的常见途径。基于这些结果，我们通过清除自由基，抑制caspase或calpain的抑制以及添加神经营养素来研究内耳疾病的衰减。所有使用的药物都限制了毛细胞损伤和药物的组合，例如抑制自由基 +神经营养素，抑制自由基 +钙蛋白酶或caspase抑制剂，对毛细胞损伤具有更大的预防作用。基于这些基础研究，我们应用了自由基清除剂（Repamipide，Vitamin C，Glutathione），可用于较差的Meniere氏病，顺铂耳毒性和长老会。这些临床试验的结果足够揭示了听力的改善。这些结果在会议上（日本耳科学会的第13和14届会议，第62和63届日本平衡协会会议，第40届Inner Earlogology讲习班），并由10篇论文提出。