先天性自身免疫性感音神经性聋防治的实验研究

目的 探讨免疫抑制剂环磷酰胺是否可以有效地预防和治疗先天性自身免疫性感音神经性聋.方法 同种粗制内耳抗原免疫雌性豚鼠,在妊娠期间给予免疫抑制剂环磷酰胺预防,对于未给予免疫抑制的母鼠所产子鼠给予环磷酰胺治疗,观察实验动物内耳听觉功能和病理形态学变化.结果 同时给予免疫抑制的母鼠及其各自所产子鼠均未出现明显的听觉损伤和内耳病理改变;出现听觉功能障碍和内耳病理变化的子鼠经环磷酰胺治疗后,其听觉功能有所提高(主要为低频区).结论 环磷酰胺可有效地预防母体内针对内耳组织特异性自身免疫反应所造成的子鼠先天性感音神经性聋,但疗效有限.     

含抗内耳抗原特异性抗体的体液转移免疫致豚鼠先天性感音神经性聋的实验研究

目的：证实针对内耳组织抗原特异性抗体通过胎盘可造成子鼠先天性自身免疫性感音神经性聋。方法：同种粗制内耳抗原（CIEAgs）免疫豚鼠,造成自身免疫性感音神经性聋（ASNHL）动物模型。ELISA法测定示其血清抗体水平升高,耳蜗电图（ECochG）示其听神经复合动作电位和（或）耳蜗微音器电位阈值或伪阈升高。取其血清（含特异性抗内耳组织抗原抗体）持续转移免疫妊娠豚鼠,采用ECochG测试被动免疫妊娠母鼠和子鼠的听觉功能,再采用颞骨火棉胶切片和苏木精一伊红染色,光镜观察内耳组织形态学改变。结果：各组出现听觉损伤的动物是：采用ASNHL模型动物血清被动免疫的8只妊娠母鼠中有5只（7耳）和其所产子鼠8只中有6只（10耳）,采用非ASNHL模型动物血清免疫的妊娠豚鼠所产子鼠5只中有1只（2耳）。出现听力损失的被动免疫母鼠和子鼠内耳病理形态学改变主要为螺旋神经节细胞变性和Rosenthal管中炎性细胞（以单个核细胞为主）浸润,部分动物出现膜迷路积水。结论：同种体液转移免疫可造成自身免疫性内耳病变,子鼠产生听觉功能障碍主要是由于母鼠所产生的特异性抗内耳组织抗原抗体经胎盘到达子鼠体内所致。     

感音神经性聋患者内耳高分辨率CT检查内耳畸形的分类

目的 探讨感音神经性聋患者中通过颞骨高分辨率螺旋CT检查内耳畸形的检出率及分类.方法 回顾性分析近10年来5 398耳感音神经性聋患者的颞骨高分辨率螺旋CT资料,患者年龄2个月~68岁,平均17.8±3.3岁;其中单侧24耳,双侧5 374耳;平均听阈83.90±5.2 dB HL,按听力损失程度分为:轻度170耳,中度1 446耳,重度1 386耳,极重度2 396耳;参照Sennaroglu 2010分类标准分析各类内耳畸形的检出情况.结果 5 398耳感音神经性聋患耳中共检出1 640耳内耳畸形(30.38%,1 640/5 398),其中,耳蜗畸形53.66%(880/1 640),非耳蜗畸形46.34%(760/1 640);880耳耳蜗畸形中,Michel畸形5耳、耳蜗未发育23耳、共同腔畸形6耳、耳蜗发育不全畸形69耳(CH-I 19耳、CH-II 16耳、CH-III 34耳)、耳蜗分隔不全畸形777耳(IP-I 44耳、IP-II 703耳、IP-III 30耳);760耳非耳蜗畸形中,大前庭导水管680耳,单纯前庭、半规管、内听道畸形80耳.与大前庭水管相关畸形共1 383耳(IP-II型 703耳、大前庭水管680耳),占全部内耳畸形的84.33%(1 383/1 640).结论 本组感音神经性聋患者内耳畸形检出率较高,且以大前庭水管相关畸形多见,Sennaroglu2010分类方法有利于各类内耳畸形发病率的流行病学统计.     

先天性内耳畸形的人工耳蜗植入

目的 探讨先天性内耳畸形引起重度感音神经性聋者人工耳蜗植入的有关问题。方法 2001年1月至2003年4月间对内耳畸形引起极重度感音神经性聋18例进行了人工耳蜗植入术。结果 18例中前庭水管11例，Waardenburg综合征3例，Mondini畸形3例，Usher综合征1例。全部病例采用Nucleus24型人工耳蜗，其中对前庭水管5例采用Contour植入体，其余病例采用直电极植入体。术中发现前庭水管11例开骨窗后仅有外淋巴搏动，但无井喷(脑脊液漏)，电极植入顺利。Waardenburg综合征3例和Mondini畸形3例中各有1例伴发圆窗骨性封闭畸形。结论 前庭水管者人工耳蜗植入手术顺利，术后效果与耳蜗发育正常者相同。如Mondini和Common Cavity等内耳畸形者行人工耳蜗植入时术前应准确评估畸形的程度及伴发的畸形，要充分估计手术难度和避免术后可能出现的脑脊液耳鼻漏及其颅内感染。     

鼻咽癌放疗后所致内耳损伤机制及防治

鼻咽癌是我国常见的恶性肿瘤之一,放射治疗为主要治疗手段,放疗后导致高频感音神经性聋为其常见的并发症。放疗可以引起耳蜗外毛细胞形态学改变,放射性内耳损伤机制可能与耳蜗感觉细胞脂质过氧化作用及耳蜗微循环障碍相关,近来有学者发现Prestin蛋白可能参与感音神经性聋的发生,放射性内耳损伤防治方法也很少。本文将对鼻咽癌患者放疗后内耳损伤研究的文献进行综述,为鼻咽癌放疗后出现内耳损伤的特点、机制和防治提供参考。     

内耳手术听力保护及激光技术应用

传统内耳手术包括各种镫骨足板开窗手术、半规管手术、耳蜗植入等,伴随医学发展,内耳手术进一步发展,包括手术范围扩大、手术方式改良等,其中听觉功能保护是内耳手术发展的关键。传统的耳科手术电钻产生的声损伤和热损伤会影响内耳,可能造成不可逆的重度感音神经性聋。激光技术具有极低的热、声损伤等优势,可以减少内耳损伤,而且在激光骨及软组织消融过程中还可释放一系列保护性因子,透过膜迷路对耳蜗毛细胞产生保护作用,进一步保护听力,是未来内耳手术重要的发展方向。     

自身免疫性感音神经性聋体液与细胞转移免疫研究

为探讨体液和细胞转移免疫是否能造成自身免疫性感音神经性聋(autoimmune sensorineuralhearing loss.ASHL),采取ASHL模型动物的血清和T淋巴细胞进行转移免疫,观察被动免疫动物听觉功能和内耳病理形态学变化,发现体液和细胞转移免疫后,部分被动免疫动物出现不同程度的听觉损伤和内耳病理改变,两组听力损失的发生率分别为16.67%和29.17%,依据Witskey法则,进一步证实ASHL是一种客观存在的自身免疫性疾病,体液性和细胞毒性变态反应在ASHL是一种客观存在的自身免疫性疾病.体液性和细胞毒性变态反应在ASHL发病中可能均起着重要作用.     

某些感音神经性聋和眩晕的血管性内耳分区新概念

该文作者为探讨耳蜗与前庭末梢感受器的解剖一功能分区新概念，应用显微蚀刻铸模技术及扫描电镜技术对健康成年大鼠的内耳血管分布与走行进行研究，获得50张以上内耳血管模型的电镜照片。根据实验结果，作者提出将导致某些类型感喜神经性聋与眩晕的内耳缺血分为4型，I型：耳蜗上部主要血管（耳蜗固有动脉）阻塞，导致低频性感音神经性登，不伴眩晕；耳蜗支阻塞，致耳蜗底部缺血，出现ZkHZ以上高频性感音神经性聋，不件眩晕。D型：前庭耳蜗动脉阻塞，耳蜗底部、球囊和后壶腹缺血，临床表现为高频听力损失，伴有眩晕。巨型：前庭耳蜗动脉阻…     

感音神经性聋患儿中先天性内耳畸形的构成、影像学及临床听力学特征

目的:分析婴幼儿、儿童先天性感音神经性聋(SNHL)中先天性内耳畸形的构成、影像学及临床听力学特征。方法:回顾性分析2005-02-2010-01上海交通大学医学院附属上海儿童医学中心耳鼻咽喉科诊治的860例先天性SNHL患儿中,经颞骨高分辨率CT及MRI发现有先天性内耳畸形的125例(225耳)患儿的听力学及影像学资料。结果:860例先天性SNHL患儿中有先天性内耳畸形者占14.5%;累及双侧98例(78.4%),单侧27例(21.6%)。225耳中167耳(74.2%)为极重度聋,36耳(16%)为重度聋,22耳(9.8%)为中度聋。该组内耳畸形中,前庭水管扩大最多见(75.6%),其次为前庭畸形(32%),再次为耳蜗前庭畸形(23.1%)。耳蜗前庭畸形中以Mondini畸形最常见(55.8%),其次为共同腔畸形(28.9%)。累及耳蜗的内耳畸形中极重度聋者明显多于未累及耳蜗的内耳畸形中极重度聋者。结论:对了解中国婴幼儿、儿童先天性SNHL中先天性内耳畸形的构成,对先天性SNHL的病因诊断以及对包括助听器、耳蜗植入等在内的干预策略的制订及其预后有一定意义。     

豚鼠自身免疫性梅尼埃病模型的主要内耳抗原分析

目的 探寻导致豚鼠自身免疫性梅尼埃病(autoimmune Meniere's disease,AIMD)的主要内耳组织抗原成分.方法 采用同种粗制内耳抗原免疫豚鼠,观察听觉功能、前庭功能及内耳组织形态学方面的变化,判断AIMD模型与非模型动物.采用免疫印迹法(Western blotting)对比分析模型动物与非模型动物血清内针对内耳组织抗原不同成分特异性免疫反应的差异,寻找只针对AIMD模型动物的特异性成分.结果 内耳组织所含抗原成分较多,免疫后酶联免疫吸附试验(ELISA)结果显示,AIMD模型与非AIMD模型动物均不同程度地存在针对内耳组织抗原的血清抗体水平升高.听功能检测,非AIMD模型动物听力损失不明显.Western bohting结果显示,AIMD模型动物出现针对相对分子质量为68 000、58 000、42 000及28 000蛋白质成分的反应条带,而非AIMD模型动物则未显示这些条带的特异性抗原抗体反应.结论 可能只有出现针对导致内耳自身免疫性疾病的主要抗原成分的特异性免疫反应,才会造成明显的内耳免疫病理损伤和功能障碍.相对分子质量为68 000、58 000、42 000及28 000的内耳组织抗原可能是导致豚鼠自身免疫性膜迷路积水的主要抗原成分.     

Auditory function in women with autoimmune inner ear diseases and their offspring

Objective

The precise cause of congenital sensorineural hearing loss (CSNHL) is unclear in many cases. In a previous study we found that offspring from guinea pigs with autoimmune sensorineural hearing loss (ASNHL) exhibited signs of SNHL. Here we studied women with autoimmune inner ear diseases (AIED) and their offspring. Our aim was to determine if autoimmune damage may be one of the causes of CSNHL.

Methods

Thirty-eight pregnant women with AIED were recruited. Thirty-three had ASNHL; one with autoimmune delayed endolymphatic hydrops (ADEH) and four with autoimmune Meniere's disease (AIMD). The following were assessed in all women: audiogram, auditory brain stem response (ABR), otoacoustic emission (OAE), vestibular function test and presence of inner ear antigens. The following were assessed in offspring from these women: OAE, ABR and presence of inner ear antigens.

Results

Five of the 38 children born to women with AIED had SNHL (an incidence much higher than normal). OAEs were not inducible in these children shortly after birth or within 46-100 days after birth. Abnormal ABR findings were apparent in these five children and inner ear antigens were detected in three of the five children (the mother's of these children were also positive for inner ear antigens).

Conclusions

These preliminary findings suggest that the prevalence of congenital ASNHL may be increased in offspring born to women with AIED.     

Detection of humoral immune response to inner ear proteins in patients with sensorineural hearing loss]

BACKGROUND: The precise mechanism of inner ear disease is still unknown. An autoimmune reaction could be one of several possible pathogenic factors involved in progressive sensorineural hearing loss. Heat shock protein 70 is suggested to play an important role in the development of autoimmune diseases. The aim of this study is the investigation of humoral immune reactivity to inner ear components in patients with sensorineural hearing loss. METHODS: The presence of antibodies to inner ear components was determined by immuno-blotting extracted bovine or human inner ear proteins. Study groups consisted of patients with idiopathic progressive sensorineural hearing loss (group A), patients with Menière's disease (group B), patients with sudden hearing loss (group C), patients with otosclerosis (group D), patients with Cogan's disease (group E), and individuals without hearing problems (group F). RESULTS: 40% of the patients with progressive sensorineural hearing loss showed reactivity against a 68-kDa protein extracted from bovine inner ear. In contrast to this, only 5% of healthy individuals and 10% with Menière's disease showed reactivity against the 68-kDa protein from bovine inner ear or against bovine heat shock protein 70. Some of the patients who showed reactivity against bovine inner ear proteins were tested with human inner ear and human heat shock protein 70; all of these showed reactivity. Approximately 6% of the patients with sudden hearing loss (group C), otosclerosis (group D), and Cogan's disease (group E) showed reactivity to inner ear proteins. A non-specific humoral immune reaction against inner ear proteins with molecular weights of 30, 40, 50, 60, and 220 kDa was observed in all patients. DISCUSSION: These results indicate a humoral immune reactivity against heat shock protein 70, which might be responsible for the pathogenesis of progressive sensorineural hearing loss.     

不同内耳组织抗原免疫致自身免疫性感音神经性聋的研究

目的：探讨不同内耳组织抗原免疫所致内耳主要病理损伤部位和听力障碍类型。方法：采用同种螺旋韧带（ＳＬ）、基底膜（ＢＭ）、螺旋神经节（ＳＧ）组织抗原免疫豚鼠，观察内耳组织病理改变和听觉功能变化。结果：ＳＬＡｇ和ＢＭＡｇ免疫组主要表现耳蜗微音器电位阈值升高和复聪现象，以及蜗管内和血管纹的免疫炎性病理改变；ＳＧＡｇ免疫组主要表现听神经复合动作电位阈值升高和幅值降低，内耳病理变化主要位于蜗轴血管及周围和ＳＧ     

Inner ear autoantibodies in patients with rapidly progressive sensorineural hearing loss

Recognition of immune-mediated sensorineural deafness that responds to immunosuppressive therapy has led to a search for a diagnostic assay to identify inner ear autoantibodies. Without a confirmed diagnosis of autoimmune disease, many patients have undergone inappropriate immunosuppressive treatment or developed irreversible inner ear damage. Serum from patients with progressive sensorineural hearing loss (n = 54), ulcerative colitis (N = 5), normal controls (N = 14), and animals with experimental autoimmune sensorineural hearing loss (EASNHL) were analyzed by Western blot against fresh bovine inner ear antigen preparations. The hearing loss group (19 [35%]) showed a single-or double-band migrating at 68,000 molecular weight (MW), differing from the normal group (1 of 14 [7%]) which showed a similar band (P = .031). Upon analysis by two-dimensional gel electrophoresis both the EASNHL guinea pigs and a patient reacted against identical components of inner ear antigen. These results suggest an autoimmune basis for disease in patients reacting against the 68,000 MW antigen.     

自身免疫性感音神经性聋的内耳代谢与电生理研究

为探讨自身免疫性感音神经性聋（ＡＳＨＬ）的内耳病理生理学机制，采用听觉电生理技术和酶组织化学方法，观察ＡＳＨＬ模型动物的内耳生理功能与组织内主要酶活性的变化。结果示：听视经复合动作电位和耳蜗微音器电位阈值明显升高，内淋巴电位（包括负相）幅值均有不同程度的降低，并与血管纹和内淋巴囊局部组织内Ｎａ＾＋－Ｋ＾＋－ＡＴＰ酶和琥珀酸脱氢酶活性改变之间的相关性。表明自身免疫性内耳损伤，进而造成组织内相关酶代谢     

Autoimmune sensorineural hearing loss: is it still a clinical diagnosis?

Inner ear involvement with sensorineural hearing loss (SNHL) has been reported in many autoimmune disorders including ulcerative colitis. The pathogenetic mechanism of hearing loss in ulcerative colitis is thought to be immune mediated. Diagnostic tests are being developed to identify inner ear autoantibodies, that may be the cause of such hearing loss. The only test that is currently available for clinical use is the Otoblot test. This, however, tests only for antibodies against bovine heat shock protein 70 which is only one of the many cross-reacting proteins against the inner ear in suspected immune-mediated hearing loss. The clinical response to steroid therapy is thus the mainstay in the diagnosis of immune-mediated hearing loss. This paper presents a series of patients with clinically suspected autoimmune hearing loss. Diagnostic assays for this condition are discussed along with a review of the recent advances in the pathogenesis and laboratory diagnosis of immune-mediated sensorineural hearing loss.     

Establishment of immunofluorescence for the testing serum antibodies against inner ear tissues and its clinical application]

A modified Sainte-Marie technique for processing the inner ear tissues of guinea pigs was described in this paper. The inner ears were fixed over night in 95% cold ethanol, decalcified 7-10 days in 10% EDTA-Na2 at 4 degrees C, and embedded in paraffin. The deparaffinized sections were exposed 15 min in 95% ethanol precooled to 4 degrees C to fix the serum antibodies of patients and labeled antibody respectively. The sections were counterstained with Evans-blue. This method is simple, rapid, and sensitive, and antigenicity. Also, the specificity was enhanced and the preservation of fluorescence was prolonged. By means of this method, antibodies against inner ear tissue were found in the serum of 18 out of 30 patients with Meniere's disease, sudden deafness or uncertain forms of progressive sensorineural hearing loss. The results suggest that autoimmune response may play an important role in some inner ear disease.     

Influence of middle ear immune response on the immunological state and function of the inner ear.

According to clinical experience, a causative correlation between otitis media and sensorineural hearing loss is likely. During an otitis media, inflammatory mediators should be released and diffuse through the round window membrane to cause an immune response of the inner ear. Using 20 guinea pigs, an immunologically caused otitis media was induced. Auditory evoked potentials were registered by means of electrocochleography and electric response audiometry from day 0 to day 7. Each time, before and after starting the immune response serum, middle ear effusion and perilymph were sampled and the concentration of interleukin-2 (IL-2) analyzed. Decalcified temporal bones were examined immunohistochemically. In this study, IL-2 was found in the middle ear effusion and perilymph, and there was evidence of an immune response of the inner ear during an otitis media. Histological results were in close correlation with this event. Electrophysiological data showed conduction deafness and signs of sensorineural hearing loss with a maximum at day 3.