川芎嗪拮抗链霉素耳毒性作用及其离子通道机制  

Reduction of Streptomycin Ototoxicity by Tetramethylpyrazine and its Ionic Channel Mechanism

作　　者：崔桂英[1] 石丽娟[1] 汤浩[1] 

机构地区：[1]中国医科大学基础医学院生理学教研室/听觉研究室,沈阳110001

出　　处：《听力学及言语疾病杂志》2007年第2期129-131,共3页Journal of Audiology and Speech Pathology

基　　金：国家自然科学基金资助项目(编号30370475)

摘　　要：目的研究川芎嗪(tetraethylplyrazine,TMP)拮抗链霉素耳毒性作用及其对耳蜗外毛细胞外向K+通道的影响,寻求两者的相关性,旨在探讨川芎嗪拮抗耳中毒作用的离子通道机制。方法选取豚鼠60只,随机分为6组,即对照组、链霉素组、川芎嗪低浓度组、川芎嗪高浓度组、川芎嗪低浓度+链霉素组和川芎嗪高浓度+链霉素组,分别注射生理盐水(2.5ml/kg)、链霉素(450mg/kg)、川芎嗪(12mg/kg)、川芎嗪(60mg/kg)、川芎嗪(12mg/kg)+链霉素(450mg/kg)、川芎嗪(60mg/kg)+链霉素(450mg/kg),用药10天后检测各组豚鼠ABR反应阈,并采用全细胞膜片钳技术观察川芎嗪对耳蜗外毛细胞Ca2+敏感K+电流和延迟外向K+电流的影响。结果结果表明川芎嗪明显降低链霉素所致的豚鼠ABR反应阈升高,提示川芎嗪具有明显的拮抗链霉素耳毒性作用;川芎嗪能明显增大豚鼠耳蜗外毛细胞Ca2+敏感K+电流和延迟外向K+电流,并呈浓度依赖关系。结论川芎嗪可能通过增大K+通道电流而发挥其降低链霉素耳毒性作用,推测这是其抗耳毒性作用机制之一。Objective To observe the effect of tetraethylplyrazine（TMP） on outward K^＋ channel of outer hair celLs in guinea pig cochlea. Methods 60 guinea pigs were divided into 6 groups randomly in the experiment. Auditory brainstem response was used to monitor the change of ABR thresholds and patch clamp techniques to observe the effect of TMP on outward K^＋ channel. Results TMP decreased the elevated ABR threshold caused by streptomycin. The TMP increased the amplitudes of calcium sensitive potassium channels （IK（Ca）） and delayed outward potassium channels （IK） of outer hair cells of guinea pig cochlea. Conclusion The study indicates that TMP may act as a protective agent against ototoxicity of streptomycin. The amplitudes of IK（Ca）） and IK of outer hair cells are increased by the TMP, suggesting the possible mechanisms of reducing ototoxicity.

关 键 词：川芎嗪 外毛细胞 链霉素 K^+通道 

分 类 号：R764.5[医药卫生—耳鼻咽喉科]