本文選題：聽(tīng)神經(jīng)病　切入點(diǎn)：凋亡誘導(dǎo)因子　出處：《第四軍醫(yī)大學(xué)》2016年博士論文　論文類(lèi)型：學(xué)位論文

【摘要】：聽(tīng)神經(jīng)病(auditory neuropathy,AN)是臨床常見(jiàn)的一類(lèi)特殊疾病,目前被稱為聽(tīng)神經(jīng)病譜系障礙(auditory neuropathy spectrum disorder,ANSD)因其臨床癥狀特殊、發(fā)病機(jī)制不明及缺乏有效的治療手段等一直是耳鼻咽喉頭頸外科領(lǐng)域的研究熱點(diǎn)。該病最主要的聽(tīng)力學(xué)改變包括聽(tīng)腦干反應(yīng)(ABR)的缺失或嚴(yán)重波形異常,而耳蝸微音電位(CM)和耳聲發(fā)射(DPOAE)正常,鐙骨肌反射引不出或閾值升高,純音聽(tīng)力檢測(cè)多表現(xiàn)為低頻聽(tīng)閾受損。病患的首要主訴是言語(yǔ)分辨率的下降,從而導(dǎo)致的交流障礙和隨后帶來(lái)的生活困擾。表現(xiàn)特殊的聽(tīng)神經(jīng)病與常見(jiàn)的感音神經(jīng)性聾之間的明顯差別,引起了越來(lái)越多的耳鼻咽喉頭頸領(lǐng)域的專(zhuān)家們的關(guān)注。但是,我們對(duì)于該病的病因、發(fā)病機(jī)制及病變的轉(zhuǎn)歸仍然不甚明朗。因此,探索和發(fā)現(xiàn)該病的發(fā)生、發(fā)展和轉(zhuǎn)歸,既有利于深入了解聽(tīng)神經(jīng)病,也有利于我們指導(dǎo)患者的日常生活。近年來(lái),我們課題組在遲發(fā)型聽(tīng)神經(jīng)病家系中發(fā)現(xiàn)了數(shù)個(gè)新致聾基因,其中AIF表現(xiàn)為明確的X染色體隱性遺傳的特點(diǎn)。該基因的致病特點(diǎn)與目前其他已知致病基因如OTOF、DIAPH3、PJVK等所引起的先天性聽(tīng)神經(jīng)病表現(xiàn)明顯不同,我們調(diào)查的這些家系中的患者均表現(xiàn)出青春期發(fā)病的特點(diǎn),純音聽(tīng)力檢查一般表現(xiàn)為輕到中度感音神經(jīng)性耳聾。我們課題組已成功制備了AIF條件性敲除模式動(dòng)物,我們利用上述模式動(dòng)物中的一種——螺旋神經(jīng)元條件性AIF敲除動(dòng)物為模型,初步研究了AIF這個(gè)新致聾基因所編碼蛋白質(zhì)的功能,初步判斷AIF表達(dá)的缺失將導(dǎo)致耳蝸螺旋神經(jīng)元的減少及模式動(dòng)物聽(tīng)力學(xué)的改變。但其致聾機(jī)理及其它相關(guān)調(diào)控分子仍有待進(jìn)一步研究。
[Abstract]:Auditory neuropathy (AND) is a kind of common clinical special disease. It is now called auditory neuropathy neuropathy spectrum disorder ANSDs because of its special clinical symptoms. Unknown pathogenesis and lack of effective treatment have been the focus of research in the field of otolaryngology and head and neck surgery. The main audiological changes of the disease include the absence of ABR (auditory brainstem response) or severe waveform abnormalities. Cochlear microphonological potential (CMV) and otoacoustic emission (OAE) were normal, stapedius reflex could not be induced or threshold increased, pure tone audiometry was mostly characterized by impaired low frequency hearing threshold. The primary complaint of patients was the decrease of speech resolution. The obvious difference between the presence of special auditory neuropathy and the common sensorineural hearing loss has attracted the attention of more and more experts in the field of otolaryngology, head and neck. We are still not clear about the etiology, pathogenesis and outcome of the disease. Therefore, to explore and discover the occurrence, development and outcome of the disease is conducive to a deeper understanding of auditory neuropathy. In recent years, our team has discovered several new deafening genes in families with delayed auditory neuropathy. Among them, AIF is the characteristic of X chromosome recessive inheritance. The pathogenicity of this gene is obviously different from that of congenital auditory neuropathy caused by other known pathogenetic genes, such as OTOF DIAPH3, PJVK and so on. The patients in the families we investigated all showed the characteristics of puberty, pure tone hearing test generally showed mild to moderate sensorineural hearing loss. Our team has successfully prepared AIF conditioned knockout model animal. We have studied the function of AIF, a novel deafness gene encoded by a novel deafness gene, using a conditioned AIF knockout model of helical neurons in the above model animals. It is preliminarily estimated that the absence of AIF expression will lead to the decrease of spiral neurons in cochlea and the change of auditory mechanics in model animals, but the mechanism of deafness and other related regulatory molecules need to be further studied.
【學(xué)位授予單位】：第四軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類(lèi)號(hào)】：R764.43

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本文編號(hào)：1594092