【作者】 陈贤明；

【导师】 王锦玲； 姜鸿彦；

【作者基本信息】 第四军医大学 ， 耳鼻咽喉科学， 2000， 博士

【摘要】 氨基甙类抗生素（AmAn）是一类有效抗革兰阴性菌抗生素，但由于耳毒性和肾毒性，临床应用受到限制。由于该类药物耳毒性机理尚不清楚，目前尚无理想方法进行预防。庆大霉素（GM）是常用的AmAn之一，本研究从不同方面探讨了GM耳毒性机理并探讨水杨酸钠（NaSA）对GM耳毒性的拮抗作用以及新制剂水杨酸庆大霉素的耳毒性作用。 一、电子顺磁共振技术对庆大霉素及庆大霉素+水杨酸钠注射后耳蜗自由基含量的检测 电子顺磁共振（EPR）技术是直接检测自由基的唯一有效方法，本实验利用EPR技术并辅以自由基捕捉剂DMPO检测了GM及GM+NaSA注射前后豚鼠耳蜗羟自由基含量。结果：GM组耳蜗羟自由基信号较正常对照组明显增强（P＜0.05），GM+NaSA组耳蜗羟自由基信号较GM组明显减弱（P＜0.05）。结论：GM使耳蜗羟自由基含量显著增加，NaSA对GM产生的过量自由基有拮抗作用。 二、庆大霉素诱导耳蜗一氧化氮合酶（NOS）表达及一氧化氮（NO）对庆大霉素耳毒性的影响 实验用免疫组化方法检测了正常动物和GM注射动物耳蜗3型NOS的表达。结果：正常对照组耳蜗有NOS₁和NOS₃表达，NOS₁在螺旋神经节处染色较深，更多还原

【Abstract】 Aminoglycoside antibiotics (AmAn) are effective drugs in therapy against gram-negative infections, but the ototoxicity and nephrotoxicity limit their use in clinic. There aren’t effective methods to prevent the toxicity to date because of unclear mechanism. Gentamicin is one of the most used AmAn, in our studies, we investigated the mechanism of gentamicin ototoxicity in several aspects; whether sodium salicylate can prevent its ototoxicity; and the ototoxicity of salicylate gentamicin.1. Detecting free radical in the cochlea induced by gentamicin and gentamicin+ sodium salicylate with electron paramagnetic resonanceElectron paramagnetic resonance (EPR) and DMPO(a trapping agenf) were used to detect hydroxyl radical in the cochlea explanted from guinea pigs which received gentamicin and gentamicin+ sodium salicylate. Results: After gentamicin administration, the signal increased significantly(P<0.05); when sodium salicylate was injected along with gentamicin, the signal reduced(P<0.05). Conclusion: Gentamicin administration results in increment of hydroxyl radical in the cochlea of guinea pigs, sodium salicylate can inhibit this increment.2. Gentamicin induced expression of nitric oxide synthase in cochlea and nitric oxide enhanced the ototoxicity of gentamicin更多还原