The non-steroidal anti-inflammatory drugs protect mouse cochlea against acoustic injury
The non-steroidal anti-inflammatory drugs protect mouse cochlea against acoustic injury
复制标题
DOI：
10.1620/tjem.216.53
复制
发表时间：
2008-09-01
影响因子：
2.2
通讯作者：
Hara, Akira
中科院分区：
文献类型：
--
作者：
Hoshino, Tomofumi;Tabuchi, Keiji;Hara, Akira
声损伤是工业社会中人们听力损失的常见原因。环氧合酶（考克斯）和脂氧合酶（LOX）是参与花生四烯酸代谢的两种重要酶。表征了两种考克斯同工酶，考克斯-1和考克斯-2，它们在表达的调节机制方面不同。虽然考克斯-1、考克斯-2和LOX在耳蜗中有表达，但它们在耳蜗声损伤中的作用尚未得到充分评价。非甾体抗炎药（NSAID）抑制考克斯或LOX，或两者。本研究旨在评价非甾体类抗炎药对听损伤后耳蜗功能恢复的影响。将小鼠暴露于128 dB SPL（声压级）的4-kHz纯音4小时，并在声学过度暴露后接受以下药物之一2周：吲哚美辛（考克斯-1抑制剂）、美洛昔康、SC 58125和CAY 10404（考克斯-2抑制剂）以及去甲二氢愈创木酸（LOX抑制剂）。用听性脑干反应（ABR）评价过度暴露前后的听力。在声学过度暴露后一周和两周，比较对照组和药物组之间的ABR阈值变化，定义为过度暴露前后ABR阈值之间的差值。用吲哚美辛或去甲二氢愈创木酸治疗小鼠可降低过度暴露后的ABR阈值偏移，表明考克斯-1和LOX抑制剂对声损伤具有保护作用。相反，考克斯-2抑制剂美洛昔康、SC 58125和CAY 10404对ABR阈值偏移没有明显影响。提示考克斯-1和LOX参与了耳蜗声损伤的发病过程。
Acoustic Injury is a common cause of hearing loss for people in industrial societies. Cyclooxygenase (COX) and lipoxygenase (LOX) are two important enzymes involved in arachidonic acid metabolism. Two COX isozymes are characterized, COX-1 and COX-2, that differ in terms of regulatory mechanisms of expression. Although COX-1, COX-2, and LOX are expressed in cochlea, their roles played in cochlear acoustic injury have not fully been evaluated. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit either COX or LOX, or both. This Study evaluated the effects of NSAIDS on the functional recovery of the cochlea after acoustic injury. Mice were exposed to a 4-kHz pure tone of 128 dB SPL (Sound pressure level) for 4 hours and received one of the following drugs for two weeks after acoustic overexposure: indomethacin (COX-1 inhibitor), meloxicam, SC58125, and CAY10404 (COX-2 inhibitors), and nordihydroguaiaretic acid (LOX inhibitor). The hearing ability was evaluated using an auditory brainstem response (ABR) before and after overexposure. The ABR threshold shifts, defined as Subtraction between ABR thresholds before and after overexposure, were compared among the control and the medication groups at one and two weeks after acoustic overexposure. Treatment of mice with either indomethacin or nordihydroguaiaretic acid decreased the ABR threshold shifts after overexposure, indicating that COX-1 and LOX inhibitors exhibited protective effects against acoustic injury. In Contrast, COX-2 inhibitors, meloxicam, SC58125, and CAY10404, showed no noticeable effects on the ABR threshold shifts. These findings Suggest that COX-1 and LOX are involved in the pathogenesis of acoustic injury in cochlea.