本文關(guān)鍵詞： 卡那霉素 耳蝸毛細(xì)胞 螺旋神經(jīng)元 內(nèi)質(zhì)網(wǎng)應(yīng)激 caspase 12　出處：《吉林大學(xué)》2010年博士論文　論文類型：學(xué)位論文

【摘要】： 本研究通過大鼠卡那霉素耳毒性動(dòng)物模型的建立,于在體和離體培養(yǎng)條件下,采用ABR檢測、耳蝸鋪片、離體器官培養(yǎng)以及免疫組織化學(xué)染色方法,從功能和形態(tài)學(xué)兩方面分別觀察了卡那霉素對耳蝸毛細(xì)胞及螺旋神經(jīng)節(jié)神經(jīng)元細(xì)胞的毒性作用;應(yīng)用免疫熒光及Western blot等實(shí)驗(yàn)技術(shù)檢測了卡那霉素干預(yù)的耳蝸組織中caspase 12及calpain的表達(dá)情況并定量測定其表達(dá)規(guī)律;同時(shí),觀察了應(yīng)用calpain抑制劑對受損耳蝸組織毒性及caspase 12活性的影響;從分子和蛋白水平闡述了它們在卡那霉素誘導(dǎo)耳毒性中的作用機(jī)制;從而得出結(jié)博,caspase 12介導(dǎo)的內(nèi)質(zhì)網(wǎng)應(yīng)激是卡那霉素導(dǎo)致藥物性耳聾的機(jī)制之一,calpain抑制劑對卡那霉素耳毒性具有保護(hù)作用。應(yīng)用calpain抑制劑有望成為治療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.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2010
【分類號】：R764.43

【引證文獻(xiàn)】

相關(guān)博士學(xué)位論文 前1條

1 劉然;BMSCs對脊髓損傷修復(fù)及其作用機(jī)制的研究[D];吉林大學(xué);2011年

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本文編號：1535187