Paradoxical enhancement of active cochlear mechanics in long-term administration of salicylate
Paradoxical enhancement of active cochlear mechanics in long-term administration of salicylate
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DOI：
10.1152/jn.00959.2004
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发表时间：
2005-04-01
影响因子：
2.5
通讯作者：
Zhao, HB
中科院分区：
文献类型：
--
作者：
Huang, ZW;Luo, YY;Zhao, HB
阿司匹林（水杨酸盐）是临床上常用的长期用药。水杨酸盐可引起可逆性听力损失和耳鸣，并降低外毛细胞（OHC）的电活动性，而OHC能够主动增强基底膜振动并产生声发射。然而，阿司匹林的耳毒性机制仍不清楚。本实验通过测量清醒豚鼠的畸变产物耳声发射（DPOAEs）来研究长期施用水杨酸盐对耳蜗听力功能的影响。单次注射水杨酸钠（200 mg/kg）可在2 h内降低2f（1）-f（2）的三次畸变产物的振幅。在20-50 dB SPL刺激水平下，这种降低是显著的，并在8 h后恢复。然而，在每日注射水杨酸钠（200 mg/kg，b.i.d.）后，2f（1）-f（2）的失真产物逐渐增加。注入14天后，畸变产物增加约2- 3.5dBSPL。增加率约为0.2dB SPL/天。DP-I/O功能保持非线性。在40-70 dB SPL初级声强时，这种增加更大，并且是可逆的。停止水杨酸治疗4周后，增加的畸变产物恢复到最初的正常水平。恢复率为0.1 dB SPL/天。在注射生理盐水的对照动物中，DPOAE无变化。数据显示，长期服用水杨酸盐可以矛盾地增强主动耳蜗力学。这些数据还表明，水杨酸引起的耳鸣可能是在OHC水平产生的。
Aspirin (salicylate) is a common drug and frequently used long term in the clinic. It has been well documented that salicylate can cause reversible hearing loss and tinnitus and diminish outer hair cell (OHC) electromotility, which is capable of actively boosting the basilar membrane vibration and producing acoustic emission. However, aspirin's ototoxic mechanisms still remain largely unclear. In this experiment. the effects of long-term salicylate administration oil cochlear hearing functions were investigated by measuring distortion product otoacoustic emissions (DPOAEs) in awake guinea pigs. A single injection of sodium salicylate (200 mg/kg) could reduce the amplitude of the cubic distortion product of 2f(1)-f(2) within 2 h. The reduction was significant at 20-50 dB SPL stimulus levels and recovered after 8 h. However, following daily injections of sodium salicylate (200 mg/kg, b.i.d.), the distortion product of 2f(1)-f(2) progressively increased. After injection for 14 days, the distortion product increased about 2-3.5 dB SPL. The increase rate was about 0.2 dB SPL/day. The DP-I/O function remained nonlinear. The increase was greater at 40-70 dB SPL primary sound intensities and reversible. After cessation of salicylate treatment for 4 wk, the increased distortion product returned to the initial normal levels. The rate of recovery was 0.1 dB SPL/day. In the control animals with saline injection, there was no change in DPOAEs. The data revealed that long-term administration of salicylate could paradoxically enhance active cochlear mechanics. The data also suggested that salicylate-induced tinnitus might be generated at the OHC level.