三个半规管阻塞动物模型的建立

目的　旨在建立豚鼠单侧三个半规管阻塞的动物模型。方法　利用 2 0只豚鼠行单侧三个半规管阻塞 ,观察手术前后眼震电图、听性脑干反应 (auditorybrainstemresponses,ABR)、畸变产物耳声发射 (distortionproductotoacousticemissions,DPOAE)及形态学的变化 ,非手术耳作为对照。结果　豚鼠术后 1d出现自发性眼震 ,正弦摆动刺激单侧眼震反应消失 ,侧别与术侧一致 ,术后 30d左相与右相眼震反应对称。术前微量冰水灌注 ,两耳均能引出眼震 ,术后 30d做冰水实验结果为术耳未能引出眼震 ,非术耳出现正常的眼震反应。术后ABR阈值有轻度升高 ,DPOAE反应幅度无明显改变。 8只动物病理切片证实三个半规管完全阻塞而耳蜗Corti器和壶腹嵴结构正常。结论　表明三个半规管阻塞动物模型成功 ,提示三个半规管阻塞术可望成为治疗难治性外周性眩晕的安全有效、操作相对容易的手术方法。     

应用微波技术行后半规管阻塞术的实验研究

目的 :探讨应用微波技术行后半规管阻塞术的可行性。方法 :应用微波技术对 2 0只豚鼠行后半规管阻塞术 ,观察术前、术后豚鼠眼震电图 (ENG) ,听性脑干反应 (ABR)及形态学的变化。结果 :术后第 1天豚鼠正弦摆动刺激时术侧眼震反应减弱 ;术后第 3天双侧眼震恢复对称 ;术后 30 d冰水实验结果显示两耳能引出对称性眼震 ;术后 ABR阈值无明显改变 ;术后 6 0 d病理切片证实后半规管完全阻塞而耳蜗 Corti器和壶腹嵴正常。结论 :应用微波技术行后半规管阻塞术是对后半规管阻塞术的一种有意义的改进方法。     

后半规管阻塞前后豚鼠前庭及耳蜗功能的动态变化

目的 探讨机械性后半规管阻塞前后豚鼠前庭和耳蜗功能的动态变化。方法 采用２０只豚鼠建立单侧后半规管阻塞的动物模型,观察手术前后眼震电图,听性脑干反应,耳声发射等变化。结果 术后第１天,第３天豚鼠正弦摆动刺激术侧眼震反应,明显减术,术后第５天起双侧眼震恢复正常。术后早期ＡＢＲ阈值一度升高,第５天达高峰,ＡＢＲ阈值平均升高４．５ｄＢ。ＤＰＯＡＥ反应幅度无明显改变。结论 后半规管阻塞能选择性地消除后半规     

三个半规管阻塞动物模型的建立

目的 旨在建立豚鼠单侧三个半规管阻塞的动物模型。方法 利用２０只豚鼠行单侧三个半规管阻塞,观察手术前后眼震电图、听性脑干反应（ａｕｄｉｔｏｒｙ ｂｒａｉｎｓｔｅｍ ｒｅｓｐｏｎｓｅｓ,ＡＢＲ）、畸变产物耳声发射（ｄｉｓｔｏｒｔｉｏｎ ｐｒｏｄｕｃｔ ｏｔｏａｃｏｕｓｔｉｃ ｅｍｉｓｓｉｏｎ,ＤＰＯＡＥ）及形态学的变化,非手术耳作对照。结果 豚鼠术后１ｄ出现自发性眼震,正弦摆动刺激单侧眼震反应消失,     

不同方式半规管阻塞术治疗顽固性梅尼埃病疗效分析

目的通过不同方式半规管阻塞术治疗顽固性梅尼埃病的临床观察及疗效分析,对比分析不同阻塞方法对眩晕的控制及听力保留率,为梅尼埃病的个体化最佳治疗方案的选择提供依据。方法回顾性分析2010年12月至2016年1月我院328例行半规管阻塞术的梅尼埃病患者的临床资料。参照梅尼埃病的诊断依据和疗效评估(2006年,贵阳)标准,所有患者均临床诊断为单侧梅尼埃病,行规范化药物保守治疗至少1年以上,但眩晕仍反复发作。其中三个半规管阻塞术302例,两个半规管阻塞术21例,包括水平半规管联合后半规管阻塞15例,水平半规管联合上半规管阻塞6例;一个半规管阻塞术5例,均为水平半规管阻塞。采用纯音测听、前庭双温试验和颈源性前庭诱发肌源性电位(cervical vestibular evokedmyogenic potential,c VEMP)进行听力学和前庭功能评估,通过内耳MRI膜迷路水成像观察阻塞术后膜迷路的形态学改变。结果三个半规管阻塞术对眩晕控制的总有效率为98.0%(296/302),A级81.8%(247/302),B级16.2%(49/302),听力保留率70.2%(212/302);两个半规管阻塞术对眩晕控制的总有效率为85.7%(18/21),A级61.9%(13/21),B级23.8%(5/21),听力保留率76.2%(16/21);一个半规管阻塞对眩晕控制的总有效率为60.0%(3/5),A级40.0%(2/5),B级20.0%(1/5),听力保留率80.0%(4/5)。三个半规管阻塞术眩晕控制有效率高于两个半规管阻塞或一个半规管阻塞术(P<0.05)。听力保留率三组之间无明显差异(P>0.05)。结论半规管阻塞术是治疗顽固性梅尼埃病的有效方法。三个半规管阻塞术眩晕控制有效率最高。     

后半规和阻塞术对内耳功能与形态影响的实验观察

本实验对１５只豚鼠行后半规管阻塞术，术前，术后测定ＣＡＰ阈值和ＥＮＧ。并作常规火棉胶连续切片及透射电镜观察内耳形态变化。结果显示；ＣＡＰ阈值手术前，后无显著性差异；眼震持续时间，术后１周明显缩短，术后８周接近术前。术后１周，光镜下见耳蜗度圈前庭膜向蜗管内膨隆，其余结构无明显异常；     

三半规管阻塞与迷路切除术后前庭功能动态变化

目的：比较豚鼠三半规管阻塞与迷路切除术后前庭功能代偿的异同。材料与方法：将15只健康豚鼠分为2组，其中8只豚鼠行右侧三半规管阻塞术（triple semicircular canal occlusion,TCO)，7只豚鼠行右侧迷路切除术（labyruinthectomy,LE)，于术后一个月内观察豚鼠行为学及眼震电图（ENG）的动态变化，结果：发现术后第1天两组均出现自发性眼震，正弦摆动刺激术侧时未引出衣发性眼震，头向右侧偏斜并沿地面垂直轴向术侧旋转；LE组却出现番滚现象，术后第3，5，10，15，30天正弦摆动眼震试验，两组豚鼠术侧眼震均随时间的推移逐渐恢复，TCO组于15天左右向眼震基本恢复对称，而LE组至术后30天仅摆动幅度120，150度，180度左右向眼震基本对称，摆动幅度为60度，90度双向眼震反应差异仍有显著意义（P＜0．05），。另外，LE组有3只豚鼠仍存在头偏，结论：TCO组要比LE组动物恢复快，建立代偿和失平衡时间短。     

豚鼠外淋巴间隙阻断术对前庭和耳蜗的影响

对１８只白色豚鼠施行单侧外半规管外淋巴间隙阻断术。术前、后观察ＡＢＲ、旋转试验，并作火棉胶连续切片光镜检查。结果提示：手术前、后ＡＢＲ阈值经统计学处理差异无显著性，而眼震持续时间差异有显著性（术后缩短），初步表明本手术可致豚鼠前庭功能降低而未明显损伤耳蜗功能。     

半规管阻塞术

半规管阻塞术是在半规管骨管上开窗后,用骨蜡、骨屑、筋膜、生物胶或激光阻塞或阻断内淋巴流。目前应用最多的是后半规管阻塞术治疗良性位置性阵发性眩晕,其疗效已得到了肯定。在用后半规管阻塞术成功地治疗良性位置性阵发性眩晕后,有人进行了三半规管阻塞,旨在探索治疗梅尼埃病的方法。本文综述了良性位置性阵发性眩晕的特点、发病机制、半规管阻塞术的方法、与其它手术的比较、引起听力损失和保存听力的机制。     

半规管阻塞技术的初步临床应用

目的初步探讨临床应用半规管阻塞技术治疗位置性眩晕与梅尼埃病的安全性与有效性。方法回顾性分析1994-2000年间半规管阻塞技术临床应用的资料,其中,后半规管位置性眩晕2例,水平半规管位置性眩晕1例,内淋巴囊阻塞术后5年复发的梅尼埃病1例,男1例,女3例,年龄39-58岁。梅尼埃病患者行三半规管阻塞及内淋巴乳突腔分流术,位置性眩晕患者行相应的半规管阻塞术。结果位置性眩晕患者术后随访1.5-7年,全部患者位置性眩晕得到解除,术后纯音测听、中耳功能分析、听觉脑干电反应测试、耳声发射等听觉功能检查结果显示耳蜗功能与术前完全一致,水平半规管阻塞的患者双耳冷热试验结果显示手术消除了水平半规管的功能,后半规管阻塞的患者双耳冷热试验结果显示手术后以水平半规管为代表的其它前庭末梢器官的功能得到良好的保存。内淋巴囊阻塞术后5年复发的梅尼埃病患者术后随访2年,眩晕得到完全控制。结论半规管阻塞技术可有效控制位置性眩晕与梅尼埃病患者的眩晕,半规管阻塞对患者耳蜗功能及所阻塞半规管以外的其它前庭末梢器官功能没有影响,半规管阻塞技术可望成为位置性眩晕和梅尼埃病安全、有效的治疗手段,符合现代外科学对手术微创的要求。     

自身免疫性听神经病动物模型的建立及听性脑干反应和畸变产物耳声发射的变化

目的建立自身免疫性听神经病动物模型，探讨其听性脑干反应（auditory brainstem response ABR）和畸变产物耳声发射（distortion product otoacoustic emission DPOAE）的变化特征。方法选取耳廓反射正常的白色豚鼠250只，分离、电泳与纯化豚鼠螺旋神经节及蜗轴内的耳蜗神经纤维抗原，然后与等量完全弗氏佐剂免疫同种豚鼠，其中正常组10只，对照组10只，试验组50只。观察ABR、DPOAE、血清IgG水平、螺旋神经节和耳蜗核团形态学的改变、听神经抗原蛋白在螺旋神经节和耳蜗神经的表达、听神经纤维超微结构的变化。结果免疫后16只动物（32／100耳）出现听性脑干反应阈提高10～25dB，Ⅰ、Ⅲ波潜伏期延长，到免疫后第3周最为明显，随后有逐渐恢复的趋势，其中Ⅲ波潜伏期到第6周恢复正常；该组豚鼠DPOAE没有变化，动物血清IgG显著性升高，与对照组相比差异有统计学意义（F=10．03，P〈0．05）；均有不同程度的螺旋神经节细胞变性、数目减少，螺旋神经节和小血管周围有淋巴细胞浸润；听神经纤维出现脱髓鞘、髓鞘断裂等现象。豚鼠耳蜗核各亚核团平均细胞密度和细胞平均面积各组差异比较没有统计学意义；听神经蛋白完全分布于耳蜗螺旋神经节和听神经纤维组织。免疫后34只动物（68／100耳）没有出现ABR反应阈升高，血清IgG没有升高，与对照组相比差异没有统计学意义，螺旋神经节、耳蜗核团、听神经纤维超微结构没有变化。结论建立了豚鼠自身免疫性听神经病动物模型，该动物模型的ABR反应阈轻中度提高，Ⅰ、Ⅲ波有自然恢复的趋势。DPOAE没有变化。     

水杨酸钠对幼年和成年豚鼠听性脑干反应阈值及螺旋神经节谷氨酸脱羧酶表达的影响

目的 观察水杨酸钠对幼年和成年豚鼠听性脑干反应(ABR)阈值以及螺旋神经节谷氨酸脱羧酶(glutamic acid decarboxylase,GAD)表达的影响.方法 选择出生4 d的豚鼠40只和出生后1个月的成年豚鼠40只,分成4组(每组20只):幼年对照组,成年对照组,幼年水杨酸钠给药组[300 mg/(kg·d)],成年水杨酸钠给药组[300 mg/(kg·d)].给药15 d后每组随机选取10只豚鼠检测ABR阈值,采用免疫组织化学染色方法检测螺旋神经节GAD的表达.各组剩下的动物停止给药,继续喂养30 d后检测ABR阈值和螺旋神经节GAD的表达.结果 给药15 d后幼年水杨酸钠给药组和成年水杨酸钠给药组豚鼠ABR阈值较给药前以及同期对照组均有提高(P值均<0.001),停药30 d后幼年水杨酸钠给药组ABR阈值恢复到给药前水平,而成年水杨酸钠给药组仍停留在高阈值水平;水杨酸钠给药15 d后能明显下调幼年以及成年豚鼠螺旋神经节GAD蛋白表达,幼年豚鼠GAD表达水平低于成年豚鼠(t=4.7,P<0.001),停药30 d后幼年给药组螺旋神经节GAD表达恢复到同期对照组水平,而成年给药组则继续停留在低表达水平.结论 水杨酸钠在对幼年和成年豚鼠ABR阚值以及螺旋神经节GAD表达的影响上存在差异,其对幼年豚鼠的影响更为明显,但停药后幼年豚鼠较成年豚鼠更容易恢复到正常水平.     

Protection from noise-induced temporary threshold shift by D-methionine is associated with preservation of ATPase activities

OBJECTIVE: The present study was designed to test whether noise-induced temporary threshold shift (TTS) could be attenuated by D-methionine and its possible relation to the biochemical changes of cochlear lateral walls such as ATPase activities and oxidative stress in guinea pigs. DESIGN: Thirty-two normal-hearing male guinea pigs were randomly divided into saline-treated and D-methionine-treated (300 mg/kg) experimental groups. One hour after treatment, they were exposed to a continuous broadband white noise at 105 +/- 2 dB sound pressure level for 10 min, causing TTS. Each group was then divided into four subgroups based on the number of survival days after noise exposure (0, 1, 2, and 7 days). Each subgroup had four animals and eight ears included. By means of click-evoked auditory brain stem responses (ABR), auditory thresholds of guinea pigs were measured before noise exposure, immediately after noise exposure, and before killing. After animals were killed, cochlear lateral walls were immediately harvested and assayed for enzyme-specific activities of Na+, K+-ATPase and Ca2+-ATPase, lipid peroxidation, and nitric oxide. RESULTS: A 15.31 +/- 3.80 dB threshold shift was found immediately after noise exposure in saline-pretreated guinea pigs. In contrast, ABR threshold shift was significantly attenuated to 4.06 +/- 2.35 dB in D-methionine-treated animals. Furthermore, D-methionine enhanced the restoration of ABR threshold to baseline level by 1 day. In addition, noise significantly decreased Na+, K+-ATPase, and Ca2+-ATPase activities and increased lipid peroxidation and nitric oxide levels of the cochlear lateral walls. D-methionine significantly protected against all of these changes. CONCLUSIONS: Noise not only induced TTS but also inhibited ATPase activities as well as increased oxidative stress in guinea-pig cochlear lateral walls; all of these changes could be attenuated by d-methionine through its antioxidative property. These results suggest the potential usefulness of d-methionine in protecting from noise-induced ototoxicity.     

Correlation of increased activities of Na+, K+-ATPase and Ca2+-ATPase with the reversal of cisplatin ototoxicity induced by D-methionine in guinea pigs

Na(+), K(+)-ATPase and Ca(2+)-ATPase in the cochlear lateral wall play an important role in maintaining ionic homeostasis and physiologic function of the cochlea. The present study was designed to test whether the changes of Na(+), K(+)-ATPase and Ca(2+)-ATPase activities of the cochlear lateral wall and the brainstem of guinea pigs after receiving cisplatin for seven consecutive days were correlated with the altered auditory brainstem responses (ABR). Furthermore, whether a chemoprotective agent, D-methionine reversed the increased ABR threshold induced by cisplatin accompanied with the increased ATPase activities was also evaluated. The results obtained showed that cisplatin exposure caused not only a significant increase of threshold but also altered various absolute wave and interwave latencies of ABR. In addition, cisplatin significantly decreased the Na(+), K(+)-ATPase and Ca(2+)-ATPase activities in the cochlear lateral wall with a good dose-response relationship. Regression analysis indicated that an increase of ABR threshold was well correlated with a decrease of both Na(+), K(+)-ATPase and Ca(2+)-ATPase activities in the cochlear lateral wall. A chemoprotectant, D-methionine indeed reversed both abnormalities of ABR and ATPase activities in a well correlation function. The selectivity of these observed changes induced by cisplatin and D-methionine was revealed by the findings that cisplatin-treated guinea pigs had normal III-V interwave latency of ABR and no reduction of Na(+), K(+)-ATPase and Ca(2+)-ATPase specific activities in the brainstem, which is in accordance with the nonpenetrable cisplatin across the blood brain barrier. Taken all together, the present findings suggest that biochemical damage and ionic disturbance may contribute to cisplatin-induced ototoxicity to some extent, which can be reversed by d-methionine.     

肺表面活性物质对豚鼠分泌性中耳炎的治疗作用

目的:研究肺表面活性物质(PS)对豚鼠分泌性中耳炎(OME)的治疗作用,为OME的治疗探讨新途径。方法:将50只豚鼠随机分为对照组(10只)和实验组(40只),实验组豚鼠采用灭活的肺炎链球菌(KHP)鼓室内注射,建立OME的动物模型(听力下降,中耳积液);模型建立后再将其分为造模组(20耳)、造模对照组(10耳)、治疗组(24耳,向中耳腔注射0.05mlPS)和未治组(23耳,不做任何治疗)。造模5d后,耳内镜下观察鼓膜及鼓室积液的情况,检测各组豚鼠听性脑干反应(ABR)Ⅰ、Ⅲ波潜伏期及反应阈。结果:造模组豚鼠鼓室内注射KHP悬浮液5d后,鼓室出现积液,鼓膜浑浊,光锥消失;ABR反应阈由对照组的(14.00±3.08)dB提高至(45.00±5.67)dB,其差异有统计学意义(P<0.01);治疗组鼓室内注射PS7d后,鼓室积液减少或消失,反应阈由(45.00±5.67)dB降低至(23.53±6.32)dB,分别与造模组及未治组比较,差异有统计学意义(均P<0.01);未治组鼓室积液无变化,鼓膜更加浑浊,反应阈由(45.00±5.67)dB提高至(65.50±6.85)dB。结论:PS对豚鼠OME有治疗作用。     

Experimental study on the mechanism of free radical in blast trauma induced hearing loss]

The MDA content in the cochlear tissue and ABR hearing threshold were measured at different times after the explosion of the guinea pigs. Results showed that there were two high peak values. The MDA increases at one hour after explosion; at 3 and 6 days it was significantly increased (first peak); at 8 days it reduced to normal level; at 12 days it again remarkably increased (second peak). It was in accordance with ABR hearing threshold changes. This suggests that increasing oxygen free radical reaction may be one of the causes of damage in blast trauma induced hearing loss.     

头低位模拟失重状态对豚鼠耳蜗听功能与超微结构的影响

目的探讨头低位模拟失重对豚鼠耳蜗听功能与超微结构的影响。方法 22只豚鼠随机分为实验组16只和对照组6只。实验组采用头低位模拟失重法,身体纵轴与水平线呈-30°,于实验前、失重5天后即刻及脱离失重3天后分别测试豚鼠听性脑干反应(ABR),然后取耳蜗行扫描电镜和透射电镜观察。对照组不作任何处理。结果对照组豚鼠ABR反应阈为23.48±6.04dB SPL,实验组实验前为24.22±4.04,模拟失重5天后即刻ABR反应阈为41.61±7.01dB SPL,与实验前和对照组比较差异有显著统计学意义(P<0.05);脱离失重3天后实验组ABR反应阈为27.50±3.54dB SPL,与实验前相比差异无显著统计学意义(P>0.05)。扫描电镜观察发现失重5天后即刻豚鼠耳蜗内、外毛细胞散在缺失,纤毛融合、倒伏;透射电镜检查见内、外毛细胞细胞局部空泡形成,脱离失重3天后上述病变均有明显恢复,但未完全恢复正常。结论模拟失重5天即可以导致豚鼠耳蜗听觉功能和超微结构的损伤,脱离失重3天后听功能可以恢复正常,但其超微结构还没有完全恢复正常。     

电钻噪声对豚鼠听功能的影响

目的 观察耳科电钻噪声对豚鼠听功能的影响。方法 将48只豚鼠耳后切口置于电钻噪声连续暴露30分钟和60分钟,应用听性脑干反应（ABR）记录技术评价电钻噪声暴露前后不同时间豚鼠听功能的变化。结果 电钻噪声暴露后各组动物ABR阈值、潜伏期和波间期较暴露前略有升高,但无明显差异（P＞0.05）。结论 耳科电钻就当前临床应用的强度、时间及范围内来看,其噪声强度尚不会影响豚鼠的听功能。     

交叉听力对豚鼠听性脑干反应测试的影响

报告对８只听觉正常的及鼠，观察交叉听力对其耳蜗动作电位和听怀脑干反应测试结果的影响。先手术造成其左耳全聋，然后用四种方法分别记录ＡＢＲ反应阈和Ⅰ波潜伏期。结果发现，术耳虽已全聋，但该侧给声强度达１０ｄＢＨＬ以上时仍可记录到ＡＢＲ，而ＡＰ未能引出，代之出现的却是清晰的ＡＢＲ波形。     

Cochlear microinjection and its effects upon auditory function in the guinea pig

Microinjection through the round window membrane has been found to represent a method for vector delivery in intracochlear gene transfer in animal models but breaches the round window membrane, making it necessary to evaluate animals for possible postinjection hearing loss. In the present study healthy guinea pigs were evaluated for their baseline click auditory brainstem response (ABR) thresholds. Each animal was then injected with saline via the round window membrane. After 1 week auditory function was evaluated by click ABR. Animals with increased ABR thresholds were retested at 4 weeks. Animals with 1-week postoperative ABRs similar to baseline were not retested. Results showed that postoperative ABR thresholds in five animals (71%) remained unchanged from baseline, while two animals had increases of 20–¶25 dB in ABRs after 1 week but recovered baseline ABRs after 4 weeks. The mean baseline ABR threshold was ¶25.7 dB and was 27.9 dB after 1 week after injection. The difference between preoperative and 1-week postoperative averages was not significant (P = 0.707). In this preliminary study saline microinjection through the round window membrane did not cause permanent hearing loss in the guinea pigs tested, and any damage caused by microinjection appeared to be reversible.