摘要
目的通过动物实验验证广谱半胱氨酸蛋白酶抑制剂(ZVAD)是否可以保护耳蜗毛细胞免受噪声损害。方法选取三月龄健康小鼠,分为无噪声暴露组(DMSO)、单纯噪声暴露组(DMSO+Noise)及噪音+ZVAD(ZVAD+Noise)组。依照动物体重计算,按照1.5mg/kg,噪音+ZVAD动物经腹腔注射ZVAD五次,其余组动物相同时间点腹腔注射DMSO作为对照。动物经噪声暴露后,于噪声暴露后一小时处死取耳蜗基底膜铺片,在激光共聚焦显微镜下照片,检测活性半胱氨酸蛋白酶8(caspase 8)和caspase 9的表达,或于噪声暴露后两周行听力检测,观察ZVAD对噪声所致耳聋的影响。结果噪音暴露后耳蜗外毛细胞中活性caspase 8和caspase 9的表达明显增强,腹腔注射ZVAD可明显抑制两种活性caspase的表达增强。同时对于噪声引起的小鼠听力下降(ABR阈移16KHz:52.5±6.1 dB和32KHz:51.8±6.9 dB),腹腔注射ZVAD有一定的保护作用(ABR阈移16KHz:37.3±9.8 dB和32KHz:39.5±10.5 dB),ABR检测注射ZVAD的噪音暴露小鼠18KHz及32KHz听力阈移均较单纯噪音暴露组明显减小(p<0.05)。结论 ZVAD对噪声所致小鼠听力下降有一定的保护作用。
ObjectiveTo study the effects of Pan-easpase inhibitor （ZVAD） on the noise induced hearing loss. Methods Mice were divided into controls without noise exposure, noise only and noise plus ZVAD three groups. Each animal received a total of five IP injections of ZVAD at a final concentration of 1.5 mg/kg. ABR measurement was done to evaluate the protective effect of ZVAD to noise induced hearing loss. Then cleaved caspase-8 and caspase-9 were detected through surface prepara- tion samples and evaluated under laser confocal microscope. Results Noise treatment induced a significant increase in expres- sion of cleaved easpase-8 easpase-9 in OHCs on surface preparations and treatment with ZVAD significantly reduced the lev- el of noise-induced cleaved caspase-8 and caspase-9. Two weeks after noise exposure, the ABR threshold shifts of controls without noise exposure, noise plus DMSO （vehicle of ZVAD, threshold shift： 16KHz, 52.5±1：6.1 dB;32KHz, 51.8±6.9 dB）, and noise plus ZVAD （threshold shift： 16KHz, 37.3±9.8 dB;32KHz, 39.5±10.5 dB ）treatment groups differed significantly and the treatment with ZVAD significantly reduced NIHL at both 16 kHz （p 〈 0.05） and 32 kHz （p 〈 0.05）. Conclusion Pan-caspase inhibitor ZVAD blocks noise-induced activation Of caspase-8 and caspase-9. Consequently, treatment with ZVAD significant- ly reduces noise-induced threshold shifts.
出处
《中华耳科学杂志》
CSCD
北大核心
2013年第4期597-601,共5页
Chinese Journal of Otology
