XKR8基因敲除小鼠可以保护由噪声诱导的听力损伤OA
XKR8 knockout mice can protect against noise-induced hearing damage
目的:探讨XKR8基因在噪声性耳聋(noise-induced hearing loss,NIHL)中对其听力的影响.方法:选用6~8周龄XKR8纯合子小鼠(XKR8-/-,XKR8 KO)和野生型(Wild-type,WT)进行实验,并且先通过聚合酶链式反应(polymerase chain reaction,PCR)、琼脂糖凝胶电泳和蛋白免疫印迹实验(Western blot)来确定基因敲除小鼠的基因型.将小鼠分为未进行噪声暴露的 WT组和 XKR8组与进行噪声暴露的 WT-110 dB组和XKR8-110 dB组.将XKR8 KO小鼠和WT小鼠暴露于范围为8~20 kHz、强度为110 dB SPL的宽带噪声中持续2 h,在暴噪后的1、3、7、14 d时分别进行听觉脑干反应(auditory brainstem response,ABR)测听,在第 14天 ABR测听结束后将小鼠处死并取耳蜗进行铺片和解剖,通过免疫荧光染色,检测外毛细胞(outer hair cell,OHC)的形态和丢失数量.结果:基因型鉴定后,选用XKR8 KO(XKR8-/-)小鼠和WT小鼠进行实验.暴露噪声前,ABR 测听结果显示 XKR8 KO 和 WT 小鼠的基础听力差异无统计学意义(P>0.05).暴露噪声后第1天,ABR结果提示XKR8-110 dB组和WT-110 dB组的听阈达到85 dB左右;在噪声暴露后第3、7、14天,XKR8-110 dB组小鼠的听力阈值较WT-110 dB组小鼠低(P<0.05).OHC免疫荧光染色 显 示,XKR8-110 dB 组和 WT-110 dB 2 组在顶回(Apex)和中回(Middle)前段差异无统计学意义(P>0.05),而在 Middle中后段和底回(Base),XKR8-110 dB组 OHC的丢失较 WT-110 dB组少(P<0.05).结论:在噪声暴露后,XKR8 KO小鼠的听力水平优于WT小鼠,减轻了由噪声诱导的听力损伤.免疫荧光染色结果显示,XKR8 KO小鼠的OHC的丢失少于WT小鼠,减轻了由噪声诱导的OHC损伤.
Objective:To explore the impact of the XKR8 gene on hearing in noise-induced hearing loss(NIHL).Methods:In this experiment,6-8 week old XKR8 homozygous knockout mice(XKR8-/-,XKR8 KO)and wild-type(WT)mice were select-ed.Polymerase chain reaction(PCR),agarose gel electrophoresis,and Western blot were used to determine the genotype of the knockout mice.Mice were divided into non-noise-exposed WT and XKR8 groups,and noise-exposed WT-110 dB and XKR8-110 dB groups.XKR8 KO and WT mice were exposed to broadband noise with a frequency range of 8-20 kHz and an intensity of 110 dB SPL for 2 hours.Auditory brainstem response(ABR)tests were conducted at 1,3,7,14 days after noise exposure.On day 14,after ABR testing,the mice were sacrificed,and their cochleae were dissected and sectioned.Immunofluorescence staining was used to examine the morphology and loss of outer hair cell(OHC).Results:After genotyping,XKR8 KO(XKR8-/-)and WT mice were used for the experiments.ABR test results before noise exposure showed no significant difference in baseline hear-ing between XKR8 KO and WT mice(P>0.05).On day 1 after noise exposure,ABR results indicated that the hearing thresh-olds of both the XKR8-110 dB and WT-110 dB groups were around 85 dB.On days 3,7,14 after noise exposure,the hearing thresholds of the XKR8-110 dB group were lower than those of the WT-110 dB group(P<0.05).Immunofluorescence staining of OHC showed no significant difference between the XKR8-110 dB and WT-110 dB groups in the apex and middle segments(P>0.05).However,in the middle and basal segments,the XKR8-110 dB group had less OHC loss than the WT-110 dB group(P<0.05).Conclusion:After noise exposure,XKR8 KO mice exhibited superior hearing levels compared to WT mice,mitigating noise-induced hearing damage.Immunofluorescence staining revealed that XKR8 KO mice had less OHC loss than WT mice,re-ducing noise-induced OHC damage.
许禄华;范君琪;周浩;周志汉;廖康;吴满满;祝园平;姜鸿彦
海南医科大学,海南 海口 571199||海南省人民医院(海南医科大学附属海南医院)耳鼻咽喉头颈外科,海南 海口 571199海南医科大学,海南 海口 571199海南医科大学,海南 海口 571199海南医科大学,海南 海口 571199海南医科大学,海南 海口 571199海南医科大学,海南 海口 571199海南省人民医院(海南医科大学附属海南医院)耳鼻咽喉头颈外科,海南 海口 571199海南省人民医院(海南医科大学附属海南医院)耳鼻咽喉头颈外科,海南 海口 571199
医药卫生
噪声性耳聋XKR8OHC损伤听力保护
Noise-induced hearing lossXKR8OHC damageHearing protection
《海南医科大学学报》 2026 (10)
730-738,9
This study was supported by the Natural Science Foundation of Hainan Province(823RC558)Hainan Province Major Science and Technology Project(ZDKJ2021040) 海南省自然科学基金(823RC558)海南省重大科技项目(ZDKJ2021040)
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