一氧化氮合酶抑制剂在噪声性听力损伤中的保护作用

The Protective Effects of Nitric Oxide Synthase Inhibitor on the Noise-induced Hearing Loss in Acoustic Trauma

目的本实验探讨一氧化氮合酶抑制剂 N-硝基左旋精氨酸甲酯(N^G-nitro-L-arginine methyl ester,L-NAME)在噪声损伤中的作用。方法将豚鼠(体重350～400 g)随机分为无噪声对照组(n=20)、噪声+生理盐水组(n=20)、噪声+L-NAME 组(n=20)。噪声刺激(4 kHz 倍频程,115 dB SPL 5 h)结束72 h 后,测试脑干诱发电位(auditory brainstem responses,ABRs),制备耳蜗组织匀浆测 NO 的水平,用免疫组化观察诱导型一氧化氮合酶(inducible nitric oxide,iNOS)在耳蜗的活性。结果无噪声组动物听阈无明显变化;噪声刺激后生理盐水组听阈上升的幅度明显高于 L-NAME 组(P<0.05);噪声+生理盐水组耳蜗 NO 含量明显高于对照组(P<0.05)与噪声+生理盐水组相比,噪声+L-NAME 组耳蜗 NO 含量明显减少(P<0.05)。噪声刺激后,噪声+L-NAME 组iNOS 活性强度弱于生理盐水组。结论 iNOS 催化合成的 NO 参与噪声对耳蜗组织的损伤;L-NAME 可通过抑制 iNOS 活性对噪声性听力损伤(noise induced hearing loss,NIHL)发挥保护作用。

Purpose The study was aimed at exploring whether nitric oxide synthase inhibitor-N^C-nitro-L-arginine methyl ester(L-NAME)reduces hearing loss in acoustic trauma.Methods Sixty guinea pigs(350～400 g)were divided randomly into three groups(control group,noise+saline group,noise+L-NAME group).Auditory brainstem responses (ABRs)were measured before and 72 h after noise exposure(4 kHz octave band,115 dB SPL 5 h).The cochleas were made to determine the level of NO and reactive immunohistochemistry intensity of inducible nitric oxide synthase(iNOS)was observed.Results The thresholds at' hearing in the control group were relatively stable,while the hearing thresholds in the noise+saline group were significantly higher than those in the noise+L-NAME group(P<0.05).The NO level of the cochlear tissue in the noise+saline group was significantly higher than that in the control group(P<0.05),while the NO level in the noise+L-NAME group was significantly lower than that in the noise+saline group(P<0.05).The immunoreactivity of iNOS was more intense in the noise+saline group than that in the noise+L-NAME group.Conclusion Nitric oxide catalyzed by iNOS plays an important role in the formation of noise induced hearing loss(NIHL)in acoustic trauma and L-NAME reduces NIHL through inhibiting the activity of iNOS.