噪声损伤和苯扎贝特干预对豚鼠耳蜗脂肪酸转运蛋白1和4表达的影响  

Effects of Noise and Bezafibrate Intervention on the Expression of Fatty Acid Transporters 1 and 4 in Guinea Pig Cochlea

作　　者：胡一勇 石敏 杨风波 吕萍[1] 蒋晴晴 袁硕龙 张悦[2] 杨仕明[2] 于宁[2] Hu Yiyong;Shi Min;Yang Fengbo;Lyu Ping;Jiang Qingqing;Yuan Shuolong;Zhang Yue;Yang Shiming;Yu Ning(Department of Otorhinolaryngology,Affiliated Hospital of North Sichuan Medical College,Nanchong,637000,China;不详)

机构地区：[1]川北医学院附属医院耳鼻咽喉头颈外科,南充637000 [2]中国人民解放军总医院耳鼻咽喉头颈外科&解放军耳鼻咽喉研究所,国家耳鼻咽喉疾病临床医学研究中心,聋病教育部重点实验室,聋病防治北京市重点实验室

出　　处：《听力学及言语疾病杂志》2021年第2期177-183,共7页Journal of Audiology and Speech Pathology

基　　金：国家科学研究计划(2014CB943000);国家自然科学金项目(81470700H1304);四川省教育厅项目(16ZB0231);噪声课题(18-163-15-LZ-001-001-04);南充市科研战略合作项目(18SXHZ0280)。

摘　　要：目的观察豚鼠耳蜗脂肪酸转运蛋白1和4(fatty acid transport protein,FATP1,FATP 4)在噪声损伤和促脂肪酸代谢药物苯扎贝特干预前后的变化,探讨噪声性听力损失与FATP1、FATP4的关系。方法正常听力健康成年雄性Dunkin Hartley豚鼠21只随机分为对照组(15只)和干预组(6只),对照组在噪声暴露前随机选取3只(6耳)动物行耳蜗取材作为正常对照组,其余12只(24耳)与干预组(6只,12耳)一起予以白噪声(110 dB SPL,每天4小时,连续12天)暴露,干预组在噪声暴露的同时给予苯扎贝特(5 mg·kg-1·d-1)灌胃干预;在开始噪声暴露第6、12、24天行听性脑干反应(ABR)检测,采用脂肪酸特异性探针荧光标记技术检测脂类物质在豚鼠耳蜗的分布,采用免疫荧光染色技术、Western blot技术检测噪声暴露前后FATP1、PATP4在两组豚鼠耳蜗的表达变化。结果噪声暴露后对照组和干预组click声及4、8、16 kHz短纯音(tone burst)ABR(tb-ABR)反应阈较噪声暴露前显著升高,在噪声暴露的第12天,干预组4 kHz tb-ABR反应阈(16.25±5.82 dB SPL)明显低于对照组(32.27±5.92 dB SPL)(P<0.05);特异性脂肪酸探针荧光染色提示正常对照组豚鼠耳蜗脂类物质主要分布于基底膜外侧的Hensen细胞、螺旋神经节、血管纹,噪声暴露前免疫荧光染色显示FATP1主要表达于Corti器、螺旋唇,在螺旋神经节细胞、螺旋韧带、血管纹等少量表达;FATP4主要表达于耳蜗Corti器及螺旋韧带,在Corti器外侧的Hensen细胞、螺旋神经节、血管纹极少表达或不表达。噪声暴露后对照组(第12天)FATP1在Corti器、Hensen细胞、螺旋突、螺旋韧带的表达较噪声暴露前明显增加(P<0.01),对照组(第12天)和干预组(第24天)FATP4在Hensen细胞、螺旋唇、螺旋神经节的表达均较噪声暴露前明显增加(P<0.01),干预组(第24天)FATP4在血管纹的表达均较噪声暴露前增加(P<0.05),但对照组(第12天)FATP4在血管纹的表达均较噪声暴露前及�Objective To study the changes of cochlear fatty acid transporter proteins 1 and 4(FATP1,FATP 4)in guinea pigs before and after noise exposure,and to explore the relationship between noise-induced hearing loss and FATP1,FATP4.Methods Twenty-one healthy adult male Dunkin Hartley guinea pigs were selected by auditory brainstem response(ABR).They were randomly divided into control group and intervention group.In the control group,experimental animals were randomly selected to obtain cochlear before noise exposure.And white noise(110 dB SPL,4 hours per day,12 consecutive days)was exposed in the control group and intervention group.At the same time of noise exposure,bezafibrate(5 mg·kg-1·d-1)was given to the intervention group by the gavage.ABR audiometry was performed on the 6th,12th day of noise exposure and 12 days after noise exposure,and experimental animals were randomly selected to obtain cochlear at the same time.The distribution of fatty acids in the cochlea was detected by specific fatty acid probe staining,and the changes of FATP1 and FATP4 in the cochlea before and after noise exposure were detected by immunofluorescent staining,fluorescence quantification technique and western blot.Results The hearing thresholds of the control group and the intervention group were significantly higher than those before noise exposure.On the 12th day of noise exposure,the hearing thresholds of the intervention group(4 kHz16.25±5.82 dB SPL)were significantly lower than those of the control group(4 kHz32.27±5.92 dB SPL)(P<0.05).After noise exposure,the hearing thresholds of the intervention group recovered faster than that in the control group.The results of probe fluorescence staining showed that the lipid substances in normal guinea pigs cochlea were mainly distributed in Hensen cells,spiral ganglion and stria vascularis on the lateral basement membrane.Before noise exposure,the results of immunofluorescence staining showed that FATP1 was mainly expressed in Corti organ and spiral lip of cochlea,but a small amount of F

关 键 词：耳蜗 Hensen细胞 噪声性聋 脂肪酸转运蛋白 苯扎贝特 

分 类 号：R764.5[医药卫生—耳鼻咽喉科]