南方医科大学学报

南方医科大学学报 ›› 2014, Vol. 34 ›› Issue (03): 329-.

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盐酸椒苯酮胺通过降低caspase-3表达减轻庆大霉素豚鼠耳蜗损伤

陈浩，谢民强，吴剑，李威，李永贺   

  • 出版日期:2014-03-20 发布日期:2014-03-20

Peperphentonamine hydrochloride protects against gentamicin-induced cochlea damage
by lowering cochlear caspase-3 expression in guinea pigs

  • Online:2014-03-20 Published:2014-03-20

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摘要： 目的研究盐酸椒苯酮胺（PPTA）对庆大霉素耳蜗损伤的保护作用及抗凋亡机制。方法听力正常豚鼠分3组：正常组、GM
组和PPTA组。采用庆大霉素致豚鼠耳蜗损伤模型，PPTA腹腔注射，ABR 分析听力变化，Western blot 检测耳蜗组织中
caspase-3蛋白表达，TUNEL染色、扫描电镜和透射电镜观察形态学改变。结果ABR反应阈：GM组、PPTA组显著高于正常对
照组（P<0.05），PPTA组显著低于GM组；Western blot测caspase-3的表达：结果表明用药后GM组豚鼠caspase-3表达显著增加
（P<0.001），PPTA组显著高于正常组但显著低于GM组（P<0.001）；TUNEL、扫描和透射电镜观察见：GM组毛细胞损伤严重，耳
蜗螺旋器、血管纹和螺旋神经节存在大量凋亡细胞形态；而PPTA组耳蜗组织损伤较GM组明显减轻。结论PPTA可以通过降
低caspase-3蛋白表达抑制凋亡，对庆大霉素豚鼠耳蜗损伤起到保护作用。

Abstract: Objective To study the protective effect of peperphentonamine hydrochloride (PPTA) against gentamicin-induced
cochlear damage and its mechanism to inhibit cell apoptosis. Methods Guinea pigs with normal hearing were randomized into
control, gentamicin, and PPTA treatment groups, and the guinea pigs models of gentamicin-induced cochlear damage received
intraperitoneal injection of PPTA. The changes of hearing of the guinea pigs were evaluated with auditory brainstem response
(ABR) test, and the protein expression of caspase-3 in the cochlear tissue was detected using Western blotting. TUNEL staining,
scanning and transmission electron microscopy were performed to observe the morphological changes of the cochlea. Results
The threshold in ABR in PPTA treatment group was significantly higher than that in the control group (P<0.05) but
significantly lower than that in gentamicin group. Western blotting showed a significantly increased caspase-3 expression in
gentamicin group (P<0.001); caspase-3 expression in PPTA group was obviously higher than that in the control group but
much lower than that in gentamicin group (P<0.001). TUNEL assay and electron microscopy revealed serious damages of the
hair cells in gentamicin group with numerous apoptotic cells in the organ of Corti, stria vascularis and spiral ganglion, and
such cochlear damages were obviously alleviated in PPTA group. Conclusion PPTA can protect against gentamicin-induced
cochlear damage in guinea pigs by decreasing the protein expression of caspase-3 to inhibit cell apoptosis.