损毁外侧丘系背核对耳鸣小鼠下丘GAD67/NR2A表达的影响  

Effect of Lesion of the Dorsal Nucleus of Lateral Lemniscus on GAD67 and NR2A Expression in the Inferior Colliculus of Tinnitus Mice

作　　者：邬信芳 马春蕾[2] 王雁鹏 顾晓[1] 孙文凯 孙卉 高伟[1] 李钦[1] Wu Xinfang;Ma Chunlei;Wang Yanpeng;Gu Xiao;Sun Wenkai;Sun Hui;Gao Wei;Li Qin(Department of Otorhinolaryngology Head and Neck Surgery,Linyi People’s Hospital of Shandong Province,Linyi,276003,China;不详)

机构地区：[1]山东省临沂市人民医院耳鼻咽喉头颈外科,临沂267003 [2]滨州医学院神经科学研究所

出　　处：《听力学及言语疾病杂志》2023年第3期257-261,共5页Journal of Audiology and Speech Pathology

摘　　要：目的探讨外侧丘系背核(dorsal nuclei of lateral lemniscus,DNLL)在耳鸣发生中的作用及可能机制。方法选取听力正常的雄性C57B/6小鼠24只,随机分为4组,每组6只。A组每天腹腔注射水杨酸钠350 mg/kg,连续14 d;B组同A组法注射等量生理盐水;C组脑立体定位仪下右侧DNLL内注射10 mmol/L的红藻氨酸0.25μl造成化学损毁;D组同C组法注射等量生理盐水。处理前后检测各组小鼠ABR阈值、旷场、高架十字、强迫游泳、声刺激-跳杆反射等行为学指标;并于处理后第14 d,用Western blot法检测各组下丘组织中谷氨酸脱羧酶67(GAD67)、N-甲基-D-天冬氨酸受体2A(NR2A)的表达含量。结果与处理前相比较,处理后①ABR:A组小鼠纯音32、16、8 kHz和click声反应阈值均明显升高(P<0.05),C组小鼠纯音32、16 kHz反应阈值显著升高(P<0.05),B组和D组反应阈值未见明显变化;②行为学:A组和C组小鼠旷场及高架十字迷宫行为指标均明显减少,强迫游泳中不动时间明显增加,声刺激-跳杆反射中假阳性次数明显增加(P<0.05);而B组和D组上述行为学指标均无明显改变;③Western blot:A组小鼠下丘组织中GAD67表达明显降低,NR2A明显升高;C组小鼠DNLL损毁侧GAD67表达明显降低,NR2A无明显变化;DNLL未损毁侧NR2A表达明显升高,而GAD67无明显变化。结论损毁DNLL可以导致小鼠耳鸣,其机制可能是通过减少对下丘抑制性神经递质的输入以下调下丘中GAD67的表达、同时上调NR2A的表达而实现的。Objective To investigate the role and possible mechanisms of the dorsal nuclei of lateral lemniscus(DNLL)in the etiology of tinnitus.Methods A total of 24 male C57 mice with normal hearing were randomly divided into 4 groups:mice in group A were injected intraperitoneally with 350 mg/kg of sodium salicylate;mice in group B were injected intraperitoneally saline in the same way as mice in group A;mice in group C had their right DNLL injected kainic acid,via a brain stereotaxic;mice in group D were injected saline in the same way as mice in group C.After successful homozygous moulding,the mice were subjected to tests such as ABR,open field,elevated cross,forced swimming and sound avoidance reflex.They were sacrificed 14 days after the moulding.Hypothalamus glutamic acid decarboxylase 67(GAD67)was detected by Western blot.Results The results were compared before and after treatment:①The ABR thresholds of pure tone 32 kHz,16 kHz,8 kHz and click in mice in group A were significantly higher after treatment(all P values<0.05).For the mice in group C,the ABR thresholds at 32 kHz and 16 kHz were elevated after treatment and the differences were statistically significant(all P values<0.05).Mice in group B and group D showed no significant changes in their thresholds.②From the behavioral results it was concluded that the mice in group A and group C spent significantly less time in the open field and the elevated cross.However,when they were forced to swim,their immobility time was significantly higher and the differences were statistically significant(all P values<0.05).Mice in group B and group D did not show significant changes and the differences were not statistically significant.The sound-beat reflex results showed that the number of false positives was significantly higher in mice in group A and group C.The difference was statistically significant(P values<0.05).However,there was no significant change in the number of false positives in mice in group B and group D.③The results of Western blot showed that the GAD

关 键 词：耳鸣 外侧丘系背核 下丘 GAD67 NR2A 

分 类 号：R764.45[医药卫生—耳鼻咽喉科]