连翘酯苷对顺铂耳毒性防护作用的实验研究

Investigation on the Protective Effects of Forsythiaside Against Cisplatin-Induced Ototoxicity in Guinea Pigs

黄世勇;陶泽璋;肖伯奎;

1:武汉大学人民医院耳鼻咽喉-头颈外科

摘要

目的观察连翘酯苷对顺铂耳毒性的防护作用并探讨其机制。方法将42只听力正常豚鼠随机分为空白组(10只):腹腔注射生理盐水8.0 ml·kg-1·d-1,连续8天;顺铂组(16只):腹腔注射顺铂2.0 mg·kg-1·d-1,连续8天;拮抗组(16只):前2天腹腔注射连翘酯苷25.0 mg·kg-1·d-1,第3天起腹腔注射连翘酯苷后30 min,再腹腔注射顺铂2.0 mg·kg-1·d-1,连续8天。每组豚鼠首次用药前及末次用药后第二天均行ABR检测,末次检测完毕后,心脏穿刺采血检测血清总超氧化物歧化酶(total superoxide disumutase,T-SOD)活性和丙二醛(malondialdehyde,MDA)含量,最后断头处死并取耳蜗,行硝酸银染色全耳蜗铺片、耳蜗组织切片和扫描电镜观察。结果空白组、顺铂组、拮抗组用药后ABR阈值分别为7.57±4.59、41.65±6.56、30.63±5.02 dB nHL;血清T-SOD活性分别为186.18±23.46、82.61±36.12、123.53±30.76 U/ml;MDA含量分别为4.14±0.79、10.69±1.21、7.85±0.97 nmol/ml。拮抗组ABR阈值低于顺铂组(P<0.05),顺铂组血清中T-SOD活性最低,而MDA含量最高,差异有统计学意义(P<0.5)。顺铂组耳蜗外毛细胞缺失明显,平均缺失率为53.42%,毛细胞结构紊乱,血管纹紊乱、螺旋神经节细胞数减少,而拮抗组这些损害明显减轻。结论连翘酯苷在一定程度上可以防护顺铂所致的耳蜗损伤,机制可能与其清除耳蜗组织氧自由基、减少氧化应激反应有关。

关键词

顺铂;连翘酯苷;耳毒性;自由基

基金项目(Foundation):

作者

黄世勇;陶泽璋;肖伯奎;

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顺铂连翘酯苷耳毒性自由基

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黄世勇陶泽璋肖伯奎