Caspase-12介导内质网应激参与卡那霉素诱导耳毒性的研究

发布时间：2018-02-25 21:20

本文关键词： 卡那霉素耳蜗毛细胞螺旋神经元内质网应激 caspase 12　出处：《吉林大学》2010年博士论文　论文类型：学位论文

【摘要】： 本研究通过大鼠卡那霉素耳毒性动物模型的建立,于在体和离体培养条件下,采用ABR检测、耳蜗铺片、离体器官培养以及免疫组织化学染色方法,从功能和形态学两方面分别观察了卡那霉素对耳蜗毛细胞及螺旋神经节神经元细胞的毒性作用;应用免疫荧光及Western blot等实验技术检测了卡那霉素干预的耳蜗组织中caspase 12及calpain的表达情况并定量测定其表达规律;同时,观察了应用calpain抑制剂对受损耳蜗组织毒性及caspase 12活性的影响;从分子和蛋白水平阐述了它们在卡那霉素诱导耳毒性中的作用机制;从而得出结博,caspase 12介导的内质网应激是卡那霉素导致药物性耳聋的机制之一,calpain抑制剂对卡那霉素耳毒性具有保护作用。应用calpain抑制剂有望成为治疗卡那霉素耳毒性的有效手段。
[Abstract]:In this study, the animal model of kanamycin ototoxicity in rats was established. In vitro and in vitro culture, ABR detection, cochlea preparation, in vitro organ culture and immunohistochemical staining were used. The toxic effects of kanamycin on cochlear hair cells and spiral ganglion neurons were observed in terms of function and morphology. The expression of caspase 12 and calpain in the cochlea treated with kanamycin was detected by immunofluorescence and Western blot techniques. The effects of calpain inhibitor on the toxicity of damaged cochlea tissue and the activity of caspase 12 were observed, and the mechanism of their action on kanamycin induced ototoxicity was discussed from the molecular and protein levels. It is concluded that endoplasmic reticulum stress mediated by nebula caspase 12 is one of the mechanisms of kanamycin induced deafness induced by kanamycin. Calpain inhibitor has protective effect on kanamycin ototoxicity. The application of calpain inhibitor is expected to be an effective method for the treatment of kanamycin ototoxicity.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2010
【分类号】：R764.43

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