FBXO3在噪声性聋大鼠耳蜗中的表达及意义  

Cochlear Expression of FBXO3 in Noise Induced Hearing Loss in Rats and Its Significance

作　　者：方练 林碧[1] 赵晓慧 FANG Lian;LIN Bi;ZHAO Xiaohui(Department of Otolaryngology,First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China)

机构地区：[1]温州医科大学附属第一医院耳鼻喉科,温州325000

出　　处：《中华耳科学杂志》2024年第6期1001-1005,共5页Chinese Journal of Otology

基　　金：温州市科技局课题项目(Y20180165)。

摘　　要：目的探讨FBXO3和自噬相关基因在噪声性听力损失大鼠耳蜗组织中的表达及意义。方法选取耳廓反射灵敏的Wistar大鼠20只,按照背景噪音控制将大鼠随机分为噪声暴露组[暴露在以12 kHz为中心的窄频带(100 Hz宽度)、126 dB SPL的噪声中,持续2 h]和对照组(无噪声暴露),每组10只。听性脑干反应(auditory brain response,ABR)检测两组大鼠的听阈(dB SPL),Western blot检测FBXO3和LC3在耳蜗组织的蛋白表达,通过敲除HEI-OC1耳蜗毛细胞株的FBXO3基因,检测细胞株中自噬相关基因ATG5和LC3的表达。结果噪声暴露组大鼠各频率的听阈水平升高,FBXO3表达明显降低,LC3Ⅱ表达明显升高,差异有统计学意义(P<0.01),在HEI-OC1细胞株中敲除FBXO3基因后,LC3Ⅱ/LC3Ⅰ比值明显增高,差异有统计学意义(P<0.05),用MG132抑制蛋白泛素化降解后,细胞株中ATG5表达水平明显上调,差异有统计学意义(P<0.01)。结论噪声暴露后,大鼠耳蜗组织中FBXO3表达被抑制,它通过调节细胞自噬通路,提高自噬水平,可能有助于保护耳蜗细胞和减轻噪声性听力损失。Objective To investigate the expression of FBXO3 and autophagy related genes in the cochlea in rats with noise induced hearing loss and its significance.Methods Twenty Wistar rats with normal ear reflex were selected and randomly divided into a noise exposure group(narrow frequency band[100 Hz]centered around 12 kHz at 126 dB SPL for 2 hours)and a control group(no noise exposure),with 10 rats in each group.Auditory brainstem response(ABR)thresholds(dB SPL)were tested.Western blot was used to detect the protein expression of FBXO3 and LC3 in cochlear tissues.The expression of autophagy related genes ATG5 and LC3 in HEI-OC1 cochlear hair cell line was detected by knocking out the FBXO3 gene.Results In the noise exposure group,ABR thresholds increased at all frequencies,with decreased expression of FBXO3 and increased expression of LC3Ⅱ(P<0.01).With the FBXO3 gene knocked out in the hair cell line,the proportion of LC3Ⅱ/LC3Ιincreased(P<0.05).After ubiquitination and degradation of MG132 inhibitory protein,the expression level of ATG5 in the cell line increased(P<0.01).Conclusion Following noise exposure,the expression of FBXO3 in the cochlea is inhibited in rats.Regulating the autophagy pathway and increasing the autophagy level may help protect cochlear cells and reduce noise induced hearing loss.

关 键 词：自噬 噪声 耳聋 泛素化 

分 类 号：R764.433[医药卫生—耳鼻咽喉科]