Smad4 基因缺陷小鼠耳形态学改变的初步研究

目的研究Smad4基因缺陷小鼠中耳及内耳的病理形态学改变，探讨Smad4基因对中耳及内耳发育的影响。方法利用建立的Smad4基因敲除嵌合体小鼠模型，通过火棉胶包埋HE染色观察Smad4（＋/＋）与Smad4（＋／-）小鼠的情况；通过耳蜗基底膜铺片琥珀酸脱氢酶染色观察Smad4（＋／＋）与Smad4（＋／-）小鼠的耳蜗内、外毛细胞数量；应用扫描电镜观察Smad4（＋／＋）与Smad4（＋／-）小鼠的内耳超微结构。结果火棉胶包埋HE染色显示：Smad4（＋／＋）与Smad4（＋／-）小鼠耳蜗大小、耳蜗转数均未见异常，中耳鼓膜正常，听小骨锤骨、砧骨、镫骨及关节结构正常，骨细胞排列紧密，Smad4（＋／＋）与Smad4（＋／-）之间没有差异。Smad4（＋／＋）小鼠耳蜗Corti器结构完整，未圯异常，血管纹厚薄均匀，血管腔腔径大小均匀。内、外毛细胞及内外柱细胞、支持细胞无异常，螺旋神经节细胞未见缺失；Smad4（＋／-）小鼠耳蜗钩端至-回外毛细胞轮廓不清，呈均质化，细胞核消失。Deiter细胞核下沉或消失，相应的螺旋神经节细胞大量缺失。耳蜗基底膜铺片琥珀酸脱氢酶染色显示：Smad4（＋／-）和Smad4（＋／＋）小鼠均有明显的局限于Corti’S器底同的外毛细胞缺失，其中Smad4（＋／-）小鼠外毛细胞的缺失，比Smad4（＋／＋）小鼠更明显（P〈0．01），两个基因型小鼠的内毛细胞均未见缺失。扫描电镜显示：Smad4（＋／＋）小鼠未见明显病理变化，Smad4（＋／-）小鼠耳蜗钩端外毛细胞静纤毛广泛散在性缺失，外毛细胞的表皮板穿孔、自溶，其周边与指状突小皮板断离。两个基因型小鼠耳蜗内毛细胞纤毛均未见明显改变。结论Smad4基因敲除后内耳形态发生明显改变，表明Smad4基因缺陷导致小鼠内耳细胞损害。     

Smad5 基因在小鼠耳蜗胚胎发育中的作用

目的检测Smad5基因在小鼠耳蜗胚胎发育中的作用。方法选用耳廓反应灵敏、健康的C57BL／6小鼠作为种鼠交配．用观察阴栓方法获得胚胎9天到20天的胎鼠，≤17天取胚胎头，≥18天在显微镜下取耳蜗，胚胎头水平冰冻切片，耳蜗平行于蜗轴冰冻切片，HE染色方法观察小鼠内耳发育形态演变过程，免疫组织化学方法检测Smad5蛋白在小鼠胚胎10～20天的表达情况。结果胚胎10天，听泡发育，胚胎12天听泡下部有蜗管始基形成并开始发育。胚胎18天，蜗管发育了2圈，形成了可以辨认的内、外毛细胞，血管纹开始分化。Smad5在小鼠内耳胚胎发育全程均有阳性表达，且表达比较广泛，尤其早期在整个听囊均有表达。在胚胎15～17天．主要集中在即将发育成基底膜听觉感受器的部分。在胚胎发育中后期在内外毛细胞、螺旋神经节细胞、支持细胞、血管纹、基底膜、前庭膜等也有表达。结论Smad5参与小鼠耳蜗胚胎发育全过程，它可能为听觉的发生所必需的基因。     

Smad4 条件基因敲除小鼠听功能初步研究

目的对Smadd条件基因敲除后三种不同基因型小鼠野生型＋／＋、杂合子＋／-、纯合子-／-进行听功能检查。初步确定Smadd条件基因敲除后小鼠的听力学表型特征，、方法对Smad4条件基因敲除后同窝出生的三种不同基因型小鼠野生型＋／＋、杂合子＋／-、纯合子-／-分别进行听性脑干反应（ABR）和听神经复合动作电位（CAP）的检查，判断Smadd条件基困敲除后三种基因型小鼠是否有听力的改变；如果听力有所改变．再将两种方法相结合以综合判断听力改变可能的病理部位。结果各个月龄的Smadd条件基因敲除后的纯合子小鼠各频率的ABR阈值均在100dBSPL以上，有的甚至在最大给声刺激都无法引出可识别的波形。野生型和杂合子小鼠都可以诱发出可辨别、可重复的ABR波形。听神经动作电位的结果与脑干诱发电位结果相似，纯合型小鼠各个频率均未引出动作电位波形，另外两种基因型小鼠可以引出稳定的CAP波形。结论Smadd条件基因敲除后小鼠由于基因的缺陷而出现了重度感音神经性耳聋，纯合子小鼠出现全聋。     

小鼠耳蜗胚胎发育过程中Smad4基因的表达

目的探讨小鼠内耳胚胎发育演变过程，检测Smad4基凶在小鼠耳蜗中的表达情况。方法选用耳廓反应灵敏、健康的C57BL／6小鼠作为种鼠交配，用观察阴栓方法获得适龄胎鼠，≤17天取胚胎头，≥18天在显微镜下取耳蜗，胚胎头水平冰冻切片，耳蜗平行于蜗轴冰冻切片，HE染色方法观察小鼠耳蜗发育形态演变过程，免疫组织化学方法检测Smad4蛋白在小鼠胚胎10～20天耳蜗巾的表达情况。结果胚胎10天，听泡发育．胚胎12天听泡下部有蜗管始基形成并开始发育．胚胎18天，蜗管发育2圈，形成了可以辨认的内、外毛细胞．血管纹开始分化。Smad4从胚胎15天才开始表达，最初表达部位为耳蜗底转将发育成蜗轴以及柱状上皮分化为感觉细胞及支持细胞的区域，但在胚胎早期表达较弱，后期在耳蜗内广泛表达，在螺旋器、血管纹、前庭膜均有表达，且表达逐渐增强，而在蜗轴部位的表达逐渐减弱。结论Smad4在小鼠内耳分化期有阳性表达，且表达具有明显的阶段性和区域性，说明其参与内耳听觉器官的发育过程并且可能存耳蜗的形成过程中起着重要的作用。     

溶酶体神经氨酸酶基因缺乏小鼠听觉和耳形态学改变初步研究

目的研究溶酶体神经氨酸酶基因（Neul）敲除小鼠听功能和耳形态学改变，探讨唾液酸沉积症听力损害的病理生理机制。方法应用听性脑干反应测试和常规颞骨连续切片观察3周、2个月和4个月龄的Neul敲除纯合子（Neul-／-）和野生型（Neul＋／＋）小鼠听阈和光镜下外耳、中耳及内耳形态。结果3周龄的Neul-／-小鼠，短声和短音8、16及32kHz听阈（声压级）较Neul＋／＋提高50—55dB；2个月和4个月龄小鼠听阈提高60—68dB。Neul-／-小鼠3周龄即有明显的中耳和内耳改变，特别是2个月和4个月龄有显著的外耳道堵塞和严重中耳炎，听小骨和耳蜗骨壁细胞、血管纹边缘层和中间层细胞、耳蜗螺旋神经节细胞、螺旋缘纤维细胞、前庭膜、基底膜及沿前庭阶外淋巴隙的间皮细胞明显囊泡化，但Corti器细胞正常。前庭神经节细胞、壶腹嵴及球囊毛细胞和支持细胞也呈现明显囊泡化。结论溶酶体神经氨酸酶的缺乏可导致较严重的听力损害和耳形态改变；外耳道阻塞或中耳炎和听骨改变可能引起传导性聋；耳蜗螺旋神经元、血管纹、螺旋缘、前庭膜和基底膜等细胞的溶酶体储积可能导致感音神经性聋。     

Smad4基因敲除对小鼠听力和前庭功能的影响

目的研究Smad4基因敲除（Smad4＋/-）小鼠听力和前庭功能的改变.方法检测Smad4基因敲除小鼠（1、2、3、6月龄）与同种同月龄的野生型（Smad4＋/＋）小鼠的ABR阈值.按Steal的方法测定小鼠的平衡功能,包括游泳试验、空间姿势反射,以及一般行为观察.结果 2、3、6月龄Smad4＋/-小鼠听力较同种野生型小鼠明显下降,两种基因型小鼠听阈有显著性差异（P〈0.01）,但1月龄的不同基因型小鼠听力水平无统计学差异（P〉0.05）.Smad4基因敲除小鼠与野生型小鼠外观和体重无明显差异（P〉0.05）,生后至6月龄的Smad4＋/-小鼠与野生型小鼠均无前庭功能异常和行为异常.结论单倍体Smad4基因敲除小鼠听力明显障碍,但前庭功能基本正常.表明Smad4对内耳的听觉有重要作用,可能存在着单倍体功能不全性;而单倍体Smad4基因缺失对于前庭功能影响可能不明显.     

Smad4条件基因敲除小鼠内耳前庭的组织学变化

目的 观察Smad4条件基因敲除小鼠内耳前庭的组织学变化,探讨Smad4基因在内耳前庭发育中的作用.方法 应用冰冻切片、免疫荧光化学、激光扫描共聚焦显微镜、扫描电镜、透射电镜等技术,观察软骨组织Smad4条件基因敲除小鼠内耳前庭组织形态的变化.结果 Smad4 -/-小鼠内耳软骨囊Smad4免疫反应阴性,Smad4+/-小鼠阳性,Smad4+/+小鼠强阳性,而在前庭感觉上皮——壶腹嵴和囊斑里Smad4免疫反应均呈阳性,三个基因型间没有差别;通过扫描电镜和透射电镜以及神经丝免疫荧光染色观察,三个基因型小鼠内耳前庭均未发现病变.结论 Smad4条件基因敲除小鼠的内耳软骨囊里Smad4基因被有效剔除,但其对内耳前庭的组织结构和形态影响有限.     

溶酶体保护蛋白/组织蛋白酶A基因敲除小鼠听力和耳形态学初步研究

目的研究溶酶体保护蛋白/组织蛋白酶A(protective protein/cathepsin A,PPCA)基因敲除小鼠听功能和耳形态学改变,探讨半乳糖唾液酸沉积症听力损害的病理生理机制。方法应用听性脑干反应(ABR)测试和颞骨连续切片,观察1月和2月龄的PPCA基因敲除纯合子(PPCA-/-)小鼠ABR反应阈和光镜下外耳、中耳及内耳形态改变,并以野生型(PPCA / )小鼠作对照。结果1月龄PPCA-/-小鼠ABR反应阈和耳形态无明显改变;2月龄时,短声和短音8、163、2 kHz反应阈较PPCA / 提高40~45 dB SPL,中耳黏膜增厚、听骨细胞囊泡化、变形和关节腔融合,血管纹增厚、螺旋神经节细胞、螺旋缘纤维细胞、前庭膜、基底膜及沿前庭阶外淋巴隙的间皮细胞囊泡化,但Corti器毛细胞及支持细胞正常。结论溶酶体保护蛋白/组织蛋白酶A缺乏可导致听力损害、中耳及耳蜗形态改变、中耳炎、听骨改变以及耳蜗螺旋神经节、血管纹、螺旋缘、前庭膜和基底膜等细胞的溶酶体储积,可能分别是传导性聋和感觉神经性聋的形成机制。     

Smad4 条件基因敲除小鼠前庭终器形态学研究

目的研究Smad4条件基因敲除小鼠前庭终器形忿改变，探讨Smad4基因对于前庭发育的作用。方法利用建立的Smad4条件基测敲除小鼠模型．通过光镜观察Smad4（＋／＋）、Smad4（＋／-）与Smad4（-／-）三种基因型小鼠（0．5、1．5月龄）的球囊及囊斑、椭圆囊及囊斑、半规管及壶腹嵴、前庭神经节、内淋巴管与囊的形态结构、毛细胞的形态及排列缺失情况。通过扫描电镜观察球囊斑、椭圆囊斑和壶腹嵴的形态结构、毛细胞及纤毛的排列缺失情况。结果Smad4（-／-）小鼠个体及内耳明显小于Smad4（＋／＋）和Smad4（＋／-），而后面二者区别不大。所有小鼠的球囊及囊斑、椭圆囊及囊斑、半规管、前庭神经节、内淋巴管与囊的大小和结构正常，淋巴囊腔饱满，囊斑处的感觉上皮、耳石、毛细胞及纤毛排列整齐，没有发现明显的病变．三个基因型间没有差异。Smad4（-／-）小鼠壶腹嵴囊性变多且严重、后半规管壶腹嵴出现明显的副嵴、偶尔可见壶腹嵴感觉上皮空泡样变。壶腹嵴的毛细胞和支持细胞排列整齐，形态无明显改变，未见缺失。扫描电镜示球囊斑、椭圆囊斑、后、外、上半规管壶腹嵴正常，三个基因型之间没有差异。结论Smad4（-／-）小鼠的前庭终器有轻微病理改变，Smad4（＋／＋）与Smad4（＋／-）小鼠的前庭终器形态结构基本正常．表明Smad4对于前庭终器的发育影响可能不明显。     

半拷贝基因NKCC1杂合小鼠与年龄相关性听力下降的关系

目的培育杂合子NKCC1＋／一和野生型NKCC1＋／＋小鼠，观察携带不同拷贝基因的NKCC1小鼠的年龄相关性听力表现，研究NKCC1基因及其离子通道在年龄相关性听力下降（agerelated hearing loss，AHL）中的作用，并初步探讨其可能发生的机制。方法运用NKCC1＋／一杂合子小鼠和NKCC1＋／＋野生型小鼠为平台，于小鼠生长过程中的各个年龄段分别检测小鼠的听性脑干反应（auditory brainstem response，ABR）和耳蜗内电位（endocochlear potential，EP）；同时采用扫描电镜进行耳蜗形态学观察和免疫印迹杂交检测不同鼠龄小鼠耳蜗的NKCC1通道蛋白的含量。结果NKCC1＋／一杂合子小鼠与NKCC1＋／＋野生型小鼠相比较，其ABR检测短声阈值在每一年龄组的各测试频率均升高，各年龄组相比较差异有统计学意义（P值均〈0．05）。NKCC1＋／一杂合子半拷贝基因鼠的听力随年龄增长而逐渐下降，与低龄鼠相比，老龄鼠的ABR阈值显著性升高（P值均〈0．05）。NKCC1＋／-小鼠的EP也随年龄增长而呈下降趋势，老龄小鼠的EP值与其低龄鼠相比明显降低（P〈0．05）。老龄小鼠的耳蜗NKCC1蛋白含量低于低龄鼠。与老龄NKCC1＋／＋鼠相比较，老龄NKCC1＋／-鼠的耳蜗底回外毛细胞出现散在的点状缺失。结论当NKCC1基因呈现半拷贝复制时小鼠可呈现AHL，NKCC1基因可能在AHL的发病中起一定的作用。AHL的发病可能与NKCC1通道蛋白的遗传特性及功能有关，还可能与NKCC1＋／-鼠出现的耳蜗底回外毛细胞缺失有关。     

耳蜗半薄切片细胞凋亡检测

目的尝试在耳蜗半薄切片上用TUNEL方法检测耳蜗组织的细胞凋亡.方法基因敲除Smad5小鼠耳蜗,分别作常规石蜡切片和环氧树脂包埋的半薄切片,用TUNEL方法检测耳蜗组织的细胞凋亡.结果在半薄切片上Smad5基因敲除小鼠,耳蜗内有大量的凋亡细胞产生,主要集中在螺旋神经节细胞、血管纹上的细胞,以及基底膜上的间皮细胞等,而且能够更清楚的显示凋亡的毛细胞.而在石蜡切片上只在螺旋神经节细胞、血管纹上的细胞,以及基底膜上的间皮细胞检出凋亡细胞,但是毛细胞没有凋亡细胞的检出.结论用TUNEL方法检测耳蜗组织的细胞凋亡半薄切片明显好于石蜡切片.     

Time course of inner ear degeneration and deafness in mice lacking the Kir4.1 potassium channel subunit

The Kir4.1 gene (KCNJ10) encodes an inwardly rectifying K(+) channel subunit abundantly expressed in the CNS. Its expression in the mammalian inner ear has been suggested but its function in vivo in the inner ear is unknown. Because diverse human hereditary deafness syndromes are associated with mutations in K(+) channels, we examined auditory function and inner ear structure in mice with a genetically inactivated Kir4.1 K(+) channel subunit. Startle response experiments suggest that Kir4.1-/- mice are profoundly deaf, whereas Kir4.1+/- mice react like wild-type mice to acoustic stimuli. In Kir4.1-/- mice, the Reissner membrane is collapsed, the tectorial membrane is swollen, and type I hair cells and spiral ganglion neurons as well as their central processes degenerate over the first postnatal weeks. In the vestibular ganglia, neuronal cell death with apoptotic features is also observed. Immunostaining reveals that Kir4.1 is strongly expressed in stria vascularis of wild-type but not Kir4.1-/- mice. Within the spiral ganglion, Kir4.1 labeling was detected on satellite cells surrounding spiral ganglion neurons and axons. We conclude that Kir4.1 is crucial for normal development of the cochlea and hearing, via two distinct aspects of extracellular K(+) homeostasis: (1). in stria vascularis, Kir4.1 helps to generate the cochlear endolymph; and (2). in spiral and vestibular ganglia, Kir4.1 in surrounding glial cells helps to support the spiral and vestibular ganglion neurons and their projecting axons.     

Expression of vascular endothelial growth factor and its receptors in the cochlea of various experimental animals

CONCLUSION: The results of this study indicate that vascular endothelial growth factor (VEGF) may be an important regulator of the vascular network of the inner ear and suggest that the VEGF signalling pathway may play a role in pathophysiologic conditions. OBJECTIVE: In order to clarify the role of vascular growth factor in the modulation of the vascular network of the cochlea, we studied the expression of VEGF and its receptors-fms-like tyrosine kinase (Flt-1) and foetal liver kinase (Flk-1)-in the inner ear of 3-month-old rodents of different species: C57BL/6J mice, Wistar albino rats and Hartley albino guinea pigs. MATERIAL AND METHODS: Qualitative immunohistochemical studies were performed by using specific antibodies to VEGF and its receptors on paraffin sections of the cochlea. The expression levels of VEGF and its receptors were quantified by means of Western blot analysis of cochlea protein extracts. RESULTS: We demonstrated that VEGF and its receptors are expressed in the cochlea and described their distribution in the inner ear. In particular, VEGF and Flt-1 are present at the level of the modiolus, spiral ganglion, spiral ligament, basilar membrane, supporting cells, outer and inner hair cells and stria vascularis. Flk-1 was less strongly expressed in the cochlea and was not detected in the organ of Corti.     

Expression of vascular endothelial growth factor and its receptors in the cochlea of various experimental animals

Conclusion. The results of this study indicate that vascular endothelial growth factor (VEGF) may be an important regulator of the vascular network of the inner ear and suggest that the VEGF signalling pathway may play a role in pathophysiologic conditions. Objective. In order to clarify the role of vascular growth factor in the modulation of the vascular network of the cochlea, we studied the expression of VEGF and its receptors—fms-like tyrosine kinase (Flt-1) and foetal liver kinase (Flk-1)—in the inner ear of 3-month-old rodents of different species: C57BL/6J mice, Wistar albino rats and Hartley albino guinea pigs. Material and methods. Qualitative immunohistochemical studies were performed by using specific antibodies to VEGF and its receptors on paraffin sections of the cochlea. The expression levels of VEGF and its receptors were quantified by means of Western blot analysis of cochlea protein extracts. Results. We demonstrated that VEGF and its receptors are expressed in the cochlea and described their distribution in the inner ear. In particular, VEGF and Flt-1 are present at the level of the modiolus, spiral ganglion, spiral ligament, basilar membrane, supporting cells, outer and inner hair cells and stria vascularis. Flk-1 was less strongly expressed in the cochlea and was not detected in the organ of Corti.     

Expression of basement membrane type IV collagen chains during postnatal development in the murine cochlea

An immunofluorescence study was performed to examine the temporal and spatial patterns of expression for the different type IV collagen chains during postnatal cochlear development. At birth, the classical chains (4A1 and 4A2) were widely expressed, while the novel chains (4A3, 4A4, and 4A5) were completely absent. Activation of the novel chains was observed at 4 days of age, with intense, widely distributed immunostaining suggesting that most of the cells in the cochlea express the novel chains at this developmental stage. From day 8 through day 14, developmental inactivation of the novel chains results in a reduction of generalized immunoreactivity with a concomitant elevation of specific staining in the membranous structures bounding the interdental cells of the spiral limbus, the inner sulcus, the basilar membrane, and in a fibrous bed of staining radiating from the spiral prominence into the region of the spiral ligament which corresponds to the location of the root cell processes. This pattern of intense immunostaining for the novel chains persists through adulthood. The classical chains are expressed in these same anatomical regions only transiently (from day 6 to day 10), after which a gradual developmental inactivation leads to the adult expression pattern where classical collagen chains are found primarily in the perineurium, in the membranes surrounding the spiral ganglion cell bodies, and in the vascular basement membranes of the spiral ligament and the stria vascularis. The complex developmental pattern of expression for the type IV collagen chains in the murine cochlea is similar to that observed in the murine kidney, which is the other major site for basement membrane pathology in Alport syndrome.     

豚鼠耳蜗和内淋巴囊水通道蛋白的表达

目的 研究豚鼠耳蜗和内淋巴囊组织中水通道蛋白(aquaporin，AQP)不同亚型的定位表达及其意义。方法 用兔抗大鼠AQP1、AQP2、AQP3、AQP4的多克隆抗体，采用免疫组化SP法分别检测相应AQP蛋白亚型在豚鼠耳蜗和内淋巴囊组织中的表达模式。结果 在耳蜗组织中，AQP1、4广泛分布于耳蜗的各个区域，如血管纹、螺旋韧带、Corti器、螺旋缘、螺旋神经节等，AQP3除了在血管纹表达呈弱阳性外，其余区域的表达与AQP1和AQP4相似，AQP2则仅表达于Reissner膜。在内淋巴囊组织中，AQP1、AQP3和AQP4在内淋巴囊上皮细胞和上皮下纤维组织均呈强阳性表达，只是AQP3的表达强度稍弱于AQP1和AQP4，而AQP2在内淋巴囊上皮细胞和上皮下组织均呈阴性表达。结论 水通道蛋白1、3、4以相似的方式广泛分布于豚鼠耳蜗和内淋巴囊组织中，而AQP2则仅表达于Reissner膜，提示不同亚型的AQP可能在不同区域协同作用参与内淋巴的调节，从而保持内耳内环境的稳定。     

Age-related morphological changes in the basement membrane in the stria vascularis of C57BL/6 mice

Basement membrane anionic sites (BMAS) are involved in the selective transport of electrically charged macromolecules in cochlear capillaries. Using cationic polyethyleneimine (PEI), we examined age-related changes in BMAS in the cochleae of C57BL/6 mice. The mice were grouped according to age as follows: 3 days, 4 weeks, 8 weeks, 6 months, and 12 months. In the right bony labyrinths, widths of the stria vascularis were measured in paraffin-embedded sections using light microscopy. The left bony labyrinths were immersed in a 0.5 % cationic PEI solution and embedded in epoxy resin. Ultrathin sections of the left cochlea were examined using transmission electron microscopy. A significant difference in stria vascularis width was observed between the 4-week-old and 12-month-old mice. The PEI distribution in the capillary and epithelial basement membranes (BMs) of the cochlea was observed. In all animals, PEI particles were evenly distributed in the capillary BM of the spiral ligament and in the subepithelial BM of Reissner’s membrane. In the stria vascularis, PEI particles were evenly distributed in the capillary BM in 3-day-old mice. In 4- and 8-week-old mice, PEI particle sizes were markedly lower than those observed in 3-day-old mice. In 6- and 12-month-old mice, PEI particles were hardly detected in the strial capillary BM. In the strial capillary BM in these mice, the laminae rarae externa and interna disappeared, but the lamina densa became larger. We speculated that age-related changes of strial capillary BMAS may affect electrically charged macromolecule transport systems in the stria vascularis of C57BL/6 mice.     

晚期糖基化终产物受体在小鼠耳蜗中表达的初步探讨

目的通过研究晚期糖基化终产物受体(RAGE)在小鼠耳蜗中的表达,初步探讨RAGE与老年性聋关系。方法将C57BL/6J小鼠分为2月龄、10月龄组,分别行ABR阈值检测,组织学切片观察耳蜗形态结构,免疫组化和realtime PCR检测RAGE在耳蜗中的定位和定量表达,半定量RT-PCR检测其配体S100B在耳蜗中的表达情况。结果 :(1)10月龄小鼠较2月龄ABR阈值明显提高;(2)RAGE主要在两组小鼠耳蜗的螺旋神经节细胞,内外毛细胞和血管纹中表达,10月龄C57BL/6J小鼠耳蜗中RAGE平均光密度值比2月龄小鼠大,两组间差异有统计学意义;(3)2月龄组耳蜗中RAGE相对表达量为1±0.15,10月龄组小鼠耳蜗中RAGE相对表达量为2.0816±0.117,两组间差异有统计学意义;(4)配体S100B在10月龄小鼠耳蜗中表达增高。结论 RAGE在C57BL/6J小鼠耳蜗中有表达且随年龄增大表达增强,可能与配体S100B相互作用导致听力下降,提示RAGE可能与老年性聋的发病机制有关。