间隙前抑制声音惊跳反射评价耳鸣小鼠的方法改进  

Improvement of Gap-Prepulse Inhibition of Acoustic Startle in Evaluation of Tinnitus in Mice

作　　者：滕琪 梁文琦 李阳[1,2] 于倩茹[1,2] 王天颖 刘珊 李重慧 周璇 龚树生 柳柯[1,2] TENG Qi;LIANG Wenqi;LI Yang;YU Qianru;WANG Tianying;LIU Shan;LI Chonghui;ZHOU Xuan;GONG Shusheng;LIU Ke(Department of Otorhinolaryngology-Head and Neck Surgery,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China)

机构地区：[1]首都医科大学附属北京友谊医院耳鼻咽喉头颈外科,北京100050 [2]首都医科大学耳聋疾病临床诊疗与研究中心

出　　处：《中华耳科学杂志》2025年第1期108-112,共5页Chinese Journal of Otology

基　　金：国家自然科学基金项目(82371151,82071037);北京市教育委员会科研计划项目资助(KZ20231002542);首都医学科学创新中心科研培育项目资助(CX24PY14)。

摘　　要：目的改进间隙前抑制声音惊跳反射(gap-prepulse inhibition of acoustic startle,GPIAS)评价耳鸣小鼠模型的方法,建立更为稳定、可靠的小鼠耳鸣行为学评价方法。方法选用6周龄C57BL/6J雄性小鼠,随机分为对照组和噪声组。在第1、7天对对照组小鼠进行GPIAS测试,计算GPIAS差值,根据数据波动范围确定“耳鸣阈值”,应用此阈值筛选噪声组耳鸣小鼠,并应用该阈值分析对照组数据,评估假阳性率。结果对照组小鼠第1天GPIAS与第7天GPIAS差值符合正态分布,耳鸣阈值2δ为0.16。噪声后1 d,噪声组小鼠在4、8、12、16 kHz处ABR阈值均高于噪声前,差异有统计学意义(P<0.05);噪声后7 d,噪声组小鼠在4、8、12、16 kHz处ABR阈值与噪声前比较,差异均无统计学意义(P>0.05)。噪声后7 d,发生耳鸣7只。耳鸣小鼠噪声后16 kHz处GPIAS%低于噪声前,差异有统计学意义(P<0.01),4、8、12 kHz处GPIAS%与噪声前比较,差异无统计学意义(P>0.05)。耳鸣小鼠噪声后4、8、12、16 kHz处前脉冲抑制(prepulse inhibition,PPI)%与噪声前比较,差异无统计学意义(P>0.05)。噪声后无耳鸣小鼠4、8、12、16 kHz处GPIAS%、PPI%与噪声前比较,差异均无统计学意义(P>0.05)。噪声后1、7 d,对照组1只小鼠在8 kHz处GPIAS%下降幅度超过该耳鸣阈值,即发生假阳性,假阳性率6.67%。结论改进后的GPIAS评价方法可筛选出稳定、可靠的耳鸣小鼠模型,具有较高的准确性。Objective To construct a more stable and reliable mouse tinnitus model by improving the gapprepulse inhibition of acoustic startle(GPIAS)models.Methods Six-weeks-old male C57BL/6J mice were randomly divided into a control and a noise exposure group.GPIAS was evaluated on days 1 and 7 in the control group and the difference calculated.The"tinnitus threshold"was determined based on the range of data fluctuation,which was applied to screen for tinnitus in the noise exposure group,and applied to control group data for the rate of false positive.Results The difference in GPIAS between day 1 and day 7 in the control group showed a normal distribution,with the tinnitus threshold calculated at 2δ=0.16.ABR thresholds at 4,8,12 and 16 kHz were elevated on day 1 after noise exposure(P<0.05),but not on day 7(P>0.05).On day 7 after noise exposure,7 animals showed GPIAS suggesting tinnitus,with reduced GPIAS%at 16 kHz compared to before noise exposure(P<0.01),but not at 4,8 and 12 kHz(P>0.05)nor with PPI%at 4,8,12 and 16kHz(P>0.05).GPIAS%and PPI%at 4,8,12 and 16 kHz showed no significant change in non-tinnitus mice after noise compared with before noise(P>0.05).On both day 1 and 7,one mouse in the control group demonstrated decreased GPIAS%more than the tinnitus threshold at 8 kHz,representing a rate of false positive at 6.67%.Conclusion The improved GPIAS evaluation can consistently and reliably identify tinnitus in mouse model with high accuracy.

关 键 词：耳鸣评价 耳鸣小鼠 间隙前抑制声音惊跳反射 

分 类 号：R76[医药卫生—耳鼻咽喉科]