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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

本研究的目的是探讨自由基（NO、ROS）和细胞凋亡在内耳疾病中的作用，并通过调节和/或抑制内耳疾病发病机制的各个环节，从而开发治疗内耳疾病的新方法。随后，感觉细胞开始凋亡死亡。钙蛋白酶和半胱氨酸蛋白酶可能在细胞凋亡中起重要作用。这些机制被认为是几乎所有内耳疾病的共同途径。基于这些结果，我们研究了通过清除自由基、抑制半胱天冬酶或钙蛋白酶以及添加神经营养素来减轻内耳疾病。所用药物均能限制毛细胞损伤，联合用药如抑制自由基+神经营养素、抑制自由基+钙蛋白酶或半胱天冬酶抑制剂对毛细胞损伤有明显的预防作用。基于这些基础研究，我们将自由基清除剂（瑞巴派特、维生素C、谷胱甘肽）应用于控制较差的梅尼埃病、顺铂耳毒性和老年性聋。这些临床试验的结果充分显示了听力的改善。这些结果在会议上（日本耳科学会第13次和第14次会议，日本平衡研究学会第62次和第63次会议，第40次内耳生物学研讨会）发表，并发表了10篇论文