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北京市自然科学基金(5122040)

作品数:9 被引量:24H指数:2
相关作者:柳柯杨仕明施磊石闯姜学钧更多>>
相关机构:中国人民解放军总医院中国医科大学附属第一医院川北医学院附属医院更多>>
发文基金:中国博士后科学基金北京市自然科学基金国家自然科学基金更多>>
相关领域:医药卫生更多>>

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耳毒性药物对小鼠耳蜗外毛细胞prestin表达的影响被引量:6
2013年
目的探讨氨基糖甙类药物庆大霉素对小鼠外毛细胞马达蛋白prestin的影响以及和听力损害之间的关系。方法选择鼠龄为5周的C57BL/6J小鼠,每天腹腔注射庆大霉素1次,药物浓度为100mg/kg,连续给药14d。实验期间,分别在第4d,7d和第14d时检测受试小鼠的ABR(Click)以观察耳毒性药物对小鼠听功能的影响,并以未进行腹腔注射给药的小鼠(0d)作为对照组。采用免疫组织化学结合激光共聚焦显微镜方法,观察小鼠耳蜗基底膜铺片标本上prestin表达变化,并采用比较荧光强度的方法定量分析prestin在各组之间表达量的差异。结果听功能检测显示,实验组小鼠听力在第4d时开始下降,到第7d时下降达到峰值(P<0.01),14d时较第7d有所降低但无显著差异(P>0.05),但仍高于对照组(P<0.05)。prestin在外毛细胞表达量在第4d开始上调,表现为圆环状的绿色荧光变得模糊,第7d时圆环的形状已经变得不规则并且多带有比较长的尾迹,而prestin表达量达到了最高水平(P<0.01),第14d时表达量和第7d相比有所降低(P<0.05),但是仍然高于对照组(P<0.05)。结论氨基糖甙类耳毒性药物持续暴露导致prestin过表达,与小鼠的听力损害过程存在一致性,提示prestin过表达可能参与致聋过程。
赵宁柳柯杨仕明王小宇石闯施磊姜学钧
关键词:耳蜗外毛细胞PRESTIN小鼠
小鼠耳蜗内外毛细胞胞吞功能的实验研究被引量:2
2015年
目的研究小鼠内外毛细胞胞吞功能的异同,探讨毛细胞胞吞功能与动物听功能之间的关系。方法选择出生后1月龄的正常C57BL/6J小鼠耳蜗基底膜在体外培养,以染料FM1-43为胞吞示踪剂,应用活细胞成像技术观察耳蜗内外毛细胞胞吞现象。结果内毛细胞的胞吞活动主要集中在细胞底部及核下区,而外毛细胞的胞吞活动则主要集中在核上区和外侧壁区。而且,在不同的观察时间点上,内毛细胞对FM1-43的摄入量均显著高于外毛细胞(P<0.05)。结论内毛细胞的胞吞活动集中出现在细胞底部及核下区,说明这种胞吞活动与内毛细胞带状突触的功能密切相关;外毛细胞的胞吞活动主要出现在核上区及细胞外侧壁,表明这种活动更多参与了外毛细胞纤毛及离子通道。内毛细胞比外毛细胞具有更强大的胞吞功能,表明内毛细胞在听功能的发育和维持中发挥着更为关键的作用。
李四军柳柯唐嗣泉杨仕明
关键词:胞吞突触
THE COCHlEAR RIBBON SYNAPTIC RESPONSE TO AMINOGIYCOSIDE OTOTOXICITY IN C57BL/6J MICE被引量:1
2014年
Objective To investigate the early change of cochlear ribbon synapses on inner hair cells in response to aminoglycoside ototoxicity. Methods C57BL/6J mice received intraperitoneal injection of gentamicin (100 mg/kg/day), and the apical coil organ of Corti was examined on the 4th, 7th and 10th day (n=10). Litter-mates without gentamicin treatment served as controls (n=10). RIBEYE on the presynaptic membrane and AMPA receptors on the postsynaptic membrane were labeled with CtBP2 or GluR2/3 respectively. Three di-mension reconstruction was conducted using the 3DS MAX 8.0 software. Results There were no disruptions of outer or inner hair cells in all groups. However, the number of ribbon synapses on cochlear inner hair cells increased significantly within 7 days after gentamicin exposure (P<0.01), followed by a significant de-crease after 7 days.Conclusion During the early stage of aminoglycoside ototoxicity, increased population of cochlear ribbon synapses may indicate a significant down-regulation of synaptic function.
LIU KeZHAO NingSHI ChuangWU NanLIU HuizhanZHANG YueYANG WeiyanYANG Shiming
关键词:GENTAMICINCOCHLEA
Extrinsic sound stimulations and development of periphery auditory synapses被引量:1
2015年
The development of auditory synapses is a key process for the maturation of heating function. However, it is still on debate regaralng wnemer the development of auditory synapses is dominated by acquired sound stimulations. In this review, we summarize relevant publications in recent decades to address this issue. Most reported data suggest that extrinsic sound stimulations do affect, but not govern the development of periphery auditory synapses. Overall, periphery auditory synapses develop and mature according to its intrinsic mechanism to build up the synaptic connections between sensory neurons and/or interneurons.
Kun HouShiming YangKe Liu
关键词:COCHLEAPERIPHERYDEVELOPMENT
宽频带白噪声适度暴露对小鼠听力损害的实验研究被引量:10
2014年
目的:通过100dB SPL宽频带白噪声对成年C57小鼠进行单次2小时的暴露,观察该种噪声对小鼠听功能损害的特点。方法选取5-6周龄ABR听阈正常的C57小鼠(每组5-7只),随机分为5个实验组分别为:噪声暴露后即刻(P0)、1天(P1)、3天(P3)、7天(P7)、14天(P14)。实验组小鼠于100dB SPL宽频带白噪声环境下暴露2h,本实验采用噪声暴露前的小鼠作为对照组。每只实验小鼠分别于噪声暴露前及暴露后各时间点进行ABR阈值检测以评估听力受损情况,实验采用统计噪声暴露前、后各时间点小鼠ABR差值(阈移)的方法分析实验结果。结果噪声暴露后即刻,小鼠各频率的ABR阈移均为最大值(P〈0.01):Click(11.92±7.51dB)、4kHz(11.92±5.60dB)、8kHz(12.31±5.99dB)、16kHz (21.54±8.75dB)、32kHz(20.00±8.90dB),且在各个频率的阈移中,以16kHz及32kHz处的高频听力损失最严重,明显高于Click、4kHz及8kHz处的阈移(P〈0.05)。脱离噪声环境24小时后各频率的ABR阈移开始下降,2周以后,小鼠各频率ABR阈值均完全恢复至暴露前水平(P〉0.05):Click(1.11±6.01dB)、4kHz(1.11±3.33dB)、8kHz(1.11±4.17dB)、16kHz (1.67±4.33)、32kHz(2.78±4.41)。结论100dB SPL宽频带白噪声单次有限暴露可以造成小鼠出现一定程度的听力损害。在频率分布上,高频区域的听力损害更为明显。同时,本研究表明,这种噪声下小鼠听力损害可以表现自我主动恢复的特征。
石闯柳柯杨仕明姜学钧施磊
关键词:C57BL
庆大霉素暴露对小鼠肾脏与耳蜗功能损伤效应的对应关系研究被引量:2
2017年
目的观察氨基糖甙类药物庆大霉素进入小鼠肾脏和耳蜗毛细胞在时间和数量上的特点及肾功能和听功能损害情况。方法将18只6周龄的C57小鼠随机分为3组,分别为对照组(contr)、用药后1天组(d1)、用药后7天组(d7),每组6只动物。置备完成的Texas Red标记庆大霉素(GTTR)以100mg/kg浓度腹腔注射小鼠,1次/天,通过激光共聚焦显微镜观察荧光标记庆大霉素在各组小鼠耳蜗毛细胞和肾脏组织积蓄情况,采用Image-Pro Plus软件测算标本荧光强度值,并进一步估算各标本庆大霉素摄取情况。同时,通过生化检测和听力检测,观察用药后小鼠肾功能和听功能损害情况。结果小鼠标本荧光强度(OD)值测算结果:用药后1天,小鼠肾脏组织中庆大霉素即达到了高水平,P<0.01;与此同时,小鼠耳蜗毛细胞内虽然检测到明显的红色荧光,但是其OD值要明显低于肾脏组织。用药后7天,肾脏组织和耳蜗毛细胞的OD值均比对照组有极为显著的升高(P<0.01)。对小鼠肾功能和听力的检测显示,用药后1天小鼠血液中BUN和Scr水平即有明显升高,表明此时肾功能已受到损害;而用药后1天小鼠ABR阈值和对照组相比却未见显著升高(P>0.05),表明此时听力损害尚未显现。在用药后7天,小鼠BUN、Scr和ABR阈值水平和对照组相比均有显著改变(P<0.01)。结论和肾功能损害相比,庆大霉素对小鼠听觉损害具有时间上的滞后效应,而这种时间上的延迟反应为听力损害的临床干预提供了可能。
孙克冰柳柯
关键词:RED小鼠肾脏功能听功能
氨基糖甙类药物毒性对耳蜗内毛细胞传入神经突触后谷氨酸受体的影响被引量:2
2012年
目的 探讨氨基糖甙类耳毒性药物暴露下小鼠内毛细胞传入神经突触后谷氨酸受体表达水平的变化,以及这种变化和小鼠听功能改变之间的关系。方法 选择5周大小的C57BL/6J小鼠,每天腹腔注射庆大霉素1次,药物浓度为100mg/kg,连续给药14d,分别在第7天、第14天时检测受试小鼠的ABR(Click&Tone burst),并以未进行腹腔注射给药的小鼠(0d)作为对照组。使用抗GluR2/3抗体对小鼠基底膜铺片标本进行染色标记,以观察耳蜗内毛细胞传入神经突触后谷氨酸受体(GluR2/3)的表达情况。结果 注射庆大霉素小鼠在第7天、10天、14天时听力损失明显,听力阈值显著高于对照组(p<0.05)。应用庆大霉素后第7天和14天,耳蜗内毛细胞传入神经突触后谷氨酸受体(GluR2/3)的表达水平和对照组相比显著增高,听力损失最为严重,提示GluR2/3在突触后的过高表达和耳聋程度存在相关性。结论 氨基糖甙类耳毒性药物持续暴露可以造成耳蜗内毛细胞传入神经突触间隙内谷氨酸递质过表达,与耳聋程度呈正相关。
徐义策王雪峰柳柯施磊杨仕明
关键词:耳蜗听阈
EFFECTS OF MODERATE NOISE EXPOSURE ON HEARING FUNCTION IN C57BL/6J MICE被引量:1
2014年
Objective To study characteristics of hearing loss after exposure to moderate noise exposure in C57BL/6J mice. Methods Male C57BL/6J mice with normal hearing at age of 5-6 weeks were chosen for this study. The mice were randomly sclccted to be studied immediately after exposure (Group P0), or 1 day (Group P1), 3 days (Group P3), 7 day (Group P7) or 14 days (P14) after exposure. Their before exposure condition served as the normal control. All mice were exposed to a broad-band white noise at 100 dB SPL for 2 hours, ABR thresholds were used to estimate hearing status at each time point. Results ABR threshold elevation was seen at every tested frequency at P0 (P〈0.01). Elevation at high-frequencies (16 kHz and 32 kHz) was greater than at lower frequencies (4 kHz and 8 kHz, P〈0.05). From P1 to P14, ABR thresholds continuously improved, and there was no significant difference between P14 and before exposure (P〉0.05). Conclusion There is a frequency specific re- sponse to 100 dB SPL broad-band white noise in C57BL/6J mice, with the high-frequency being more susceptible. Hearing loss induced by moderate noise exposure appears reversible in C57BL/6J mice.
SHI ChuangSHI LeiJIANG XuejunYANG ShimingLIU Ke
LOWER DOSE OF AMINOGLYCOSIDE OTOTOXIC EXPOSURE CAUSES PRESYNAPTIC ALTERATIONS ASSOICATED WITH HEARING LOSS被引量:2
2014年
Objective To study presynaptic alternations of cochlear ribbons arising from aminoglycoside ototoxic stimuli in C57BL/6J mice. Methods Animals were injected with low dose gentamicin (100 mg/kg/day) for 14 days, From the 14th to 28th days, the mice were maintained free of gentamicin treatment. Immunohisto-chemistry labeling was employed to trace RIBEYE, a major presynaptic componment of ribbon synapses. RIBEYE/CtBP2 expression levels were assessed and compared with hearing threshold shifts. Auditory func-tion was assessed by auditory brainstem responses. The stereocilia of outer hair cells (OHCs) and IHCs was examined by scanning electron microscopy (SEM). Results Hearing thresholds were elevated with peak hearing loss observed on the 7th day after gentamicin exposure, followed by improvement after the 7th day. RIBEYE/CtBP2 expression directly correlated with observed hearing threshold shifts. Strikingly, we did not see any obvious changes in stereocilia in both OHCs and IHCs until the 28th day. Mild changes in stereocil-ia were only observed in OHCs on the 28th day. Conclusions These findings indicate that presynapse co-chlear ribbons, rather than stereocilia, may be sensitive to aminoglycoside ototoxic exposure in mice cochle-ae. A pattern of RIBEYE/CtBP2 expression changes seems to parallel hearing threshold shifts and suggests presynaptic response properties to lower dosage of aminoglycoside ototoxic stimuli.
LIU KeWANG XiaoyuLI SijunTANG SiquanXU YiceWANG XuefengSUN JianheYANG WeiyanYANG Shiming
关键词:STEREOCILIA
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