耳蜗电刺激并脑源性神经营养因子联合应用对大鼠耳蜗病理及听觉生理的影响  

Delayed electrical stimulation and BDNF application following induced deafness in rats

作　　者：蔡超[1] 倪志立[2] 张立松[1] 房高丽[1] 李永新[3] 

机构地区：[1]首都医科大学附属北京地坛医院耳鼻咽喉头颈外科,北京100015 [2]首都医科大学宣武医院耳鼻咽喉头颈外科,北京100053 [3]首都医科大学附属北京同仁医院耳鼻咽喉头颈外科耳鼻咽喉头颈科学教育部重点实验室(首都医科大学),北京100730

出　　处：《中国耳鼻咽喉头颈外科》2011年第8期440-444,共5页Chinese Archives of Otolaryngology-Head and Neck Surgery

基　　金：国家自然科学基金项目(30572028);北京市自然科学基金项目(7032008);北京市科技新星计划(9558101300)联合资助

摘　　要：目的探讨延迟给予慢性电刺激、脑源性神经营养因子(brain-derived neurotrophic factor,BDNF),以及二者联合应用对药物致聋大鼠耳蜗病理及听觉生理影响。方法药物致聋大鼠40只,随机平均分为人工外淋巴液组(artificial perilymph,AP)、BDNF组、电刺激(electrical stimulation,ES)+AP组、BDNF+ES组共4个组。药物致聋30 d后,左侧耳蜗植入动物用蜗内电极及药物灌注集成单元,并连接微渗透压泵,进行分组干预并每7 d行电诱发听性脑干反应(electrically evoked auditory brainstem response,EABR)阈值检测。干预28 d后处死动物,取耳蜗进行病理检查,观察蜗轴Rosenthal管内螺旋神经节细胞(spiral ganglion cells,SGC)胞体密度及骨螺旋板缰孔内SGC树突数量。结果①EABR阈值:与AP组比较,其他3组均降低,ES和BDNF联合应用具有协同作用。②耳蜗病理SGC胞体密度及神经纤维密度,除AP组外,其余3组均表现为实验侧较对照侧多;各组间左侧比较,其余3组均较AP组密度大,ES和BDNF联合应用具有协同作用。③EABR阈值与SGC树突及胞体变化存在函数关系,方程为T=469.222-1.561(F底L)-0.089(R2L),系数检验P值分别为0.000、0.001、0.023。结论大鼠致聋30 d后,鼓阶内慢性电刺激及BDNF持续灌注给药联合应用对SGC胞体及树突均有保护作用,并可以相应改善听觉敏感性,且二者具有协同作用;SGC胞体及树突的数量均影响听觉敏感性,后者影响更大。OBJECTIVE To determine the infiuence of delayed intervention of combination of electrical stimulation（ES）and neurotrophin application on the survival of spiral ganglion cells（SGCs）body,peripheral process and the auditory sensitivity after induced deafness in rat.METHODS The left cochlea of profoundly deafened rats was implanted with an electrode and drug-delivery system 30 days after induced deafness.BDNF or artificial perilymph（AP）was delivered continuously for 28 days.ES induced neural activity was in two cohorts（BDNF＋ES and ES＋AP）,and control animal received BDNF or AP without ES（BDNF and AP）.EABRs were recorded immediately following surgery and every 7 days.RESULTS EABR thresholds of BDNF,ES＋AP and BDNF＋ES groups were significantly less than those of AP group;Moreover,BDNF and ES had synergistic effect.The SGC and peripheral process density of left side were more than that in right side,and analysis of those of the left cochlea among the treatment groups demonstrated that those of treated groups were significantly more than those of AP group.The SGC and peripheral process density of BDNF＋ES group were significantly more than those of other 3 groups.Moreover,BDNF and ES had synergistic effect.Finally,a functional formula was established between the last EABR threshold and SGC density and process density.CONCLUSION Under the condition of delayed intervention following induced deafness of rats,it can be concluded that the combination of ES and BDNF has synergistic protective effect rather than additive effect.Both SGC body and peripheral process influence the auditory sensitivity,and the latter appears more important.

关 键 词：动物实验 听觉丧失 感音神经性 电刺激疗法 脑源性神经营养因子 电诱发听性脑干反应 螺旋神经节细胞 

分 类 号：R764[医药卫生—耳鼻咽喉科]