摘要
目的研究川芎嗪(tetraethylplyrazine,TMP)对庆大霉素(Gentamycin,GM)耳蜗毒性的抗氧化作用并探讨该机制与铜锌超氧化物歧化酶(Cu/Zn superoxide dismutase,Cu/Zn SOD或SOD1)、锰超氧化物歧化酶(Mn-superox-ide dismutase,Mn SOD或SOD2)及细胞外超氧化物歧化酶(ECSOD或SOD3)蛋白表达的关系。方法将60只听力正常成年豚鼠随机分为4组,即GM组、TMP组、GM+TMP组、对照组。GM组(15只)肌注硫酸庆大霉素120mg·kg-1·d-1,连续12天;TMP组(15只)腹腔注射盐酸川芎嗪30mg·kg-1·d-1,连续12天;GM+TMP组(15只)肌注硫酸庆大霉素120mg·kg-1·d-1及腹腔注射盐酸川芎嗪30mg·kg-1·d-1,连续12天;对照组(15只)腹腔注射与GM组等量的生理盐水2.5ml·kg-1·d-1,连续12天。每组豚鼠首次用药前及末次用药后第一天均行ABR检测。实验结束后将豚鼠断头处死并取耳蜗标本,免疫组化法对其细胞内SOD1、SOD2、SOD3蛋白表达进行定位研究。结果用药后GM组听力阈值明显升高,与正常组、GM+TMP组比较有明显差异(P<0.01),正常对照组与TMP组听力阈值用药前后相比无显著性差异(P>0.05)。耳蜗螺旋神经节处模型组和拮抗组SOD1、SOD2、SOD3阳性蛋白表达无统计学差异(P>0.05),毛细胞处拮抗组SOD1、SOD2阳性蛋白表达较模型组明显(P<0.05),SOD3阳性蛋白表达无统计学差异(P>0.05)。结论庆大霉素具有耳毒性,可导致豚鼠耳蜗毛细胞损伤,川芎嗪可通过对毛细胞处SOD1、SOD2的蛋白表达调控机制来实现抗氧化防护作用。
Objective To study the anti-oxidant effects of tetraethylplyrazine （TMP） on cochlea hair cells and spiral ganglion cells damaged by gentamycin （GM） and the relations between such effects and the expression level and activity of Cu/Zn superoxide dismutase （Cu/Zn SOD or SOD1）, Mn-superoxide dismutase （Mn SOD or SOD2） and ECSOD （SOD3）. Methods Sixty healthy guinea pigs were randomly divided into a model group （GM group）, a GM＋TMP treat- ment group, a TMP treatment group and a normal control group （n=15 in each group）. Animals in the GM group were in- jected with Gentamycin sulfate at 120 mg/kg/d; those in the TMP group were injected with TMP at 30 mg/kg/d; those in the GM＋TMP group were injected with Gentamycin sulfate and TMP with the same dosages; and those in the normal control group were injected with saline at 2.5 ml/kg/d. All animals were injected for 12 consecutive days. Before injec- tion and one day after the last injection, ABR thresholds were measured in all groups. At the end of the experiment, guin- ea pigs were sacrificed and immuno-histochemical methods were used to determine the level of SOD 1, SOD2 and SOD3 protein expression in cochlear tissues. Results After treatment, ABR thresholds in the GM group were significantly high-er than the GM＋TMP and normal control groups （P〈0.01）, while ABR thresholds in the TMP and normal control groups did not change significantly from before treatment （P〉0.05）. There were no significant differences in the expression of SOD1, SOD2 or SOD3 in spiral ganglion cells when the GM and GM＋TMP groups were compared （P〉0.05）, but the ex- pression of SOD1 and SOD2 in hair cells was different between the two groups （P〈0.05）, although SOD3 expression in hair cells was not significantly different between the two groups （P〉0.05）. Conclusions GM is ototoxic and causes co- chlea hair cell damage. TMP plays an anti-oxidant role through regulation of SOD 1, SOD2 exvression in hair ceils.
出处
《中华耳科学杂志》
CSCD
北大核心
2016年第3期408-413,共6页
Chinese Journal of Otology
