西地那非对豚鼠噪声性听觉损伤阈移的影响

Effect of sildenafil on ABR thresholds shift to noise-induced hearing loss in guinea pigs

目的探讨西地那非（sildenafil）对豚鼠噪声性听觉损伤阈移的影响。方法将豚鼠按随机数字表法分为对照组、噪声暴露组和西地那非给药组，每组10只。西地那非组及噪声组豚鼠在白噪声（A计权声压级110dB）暴露1周后分别腹腔注射西地那非10mg／（kg·d）及生理盐水4ml／（kg·d），连续给药4周。分别测试噪声暴露前1日、噪声暴露后1、2及4周听性脑干反应（ABR）阈值，并通过扫描电镜观察噪声暴露后4周豚鼠耳蜗毛细胞的形态变化。结果噪声暴露后，噪声暴露组豚鼠ABR阈值（声压级）平均提高19．1dB，随着时间推移，阈移逐渐加大，暴露后4周，阈值平均提高22．0dB；西地那非组噪声暴露后ABR阈值提高19．8dB，给药后阈移逐渐减小，给药后4周，阈值仅平均提高4．8dB。西地那非组与噪声暴露组相比，除噪声暴露结束后这一时间点以外，其余给药后各时间点ABR阈值差异均具有统计学意义（P值均〈0．05）。扫描电镜显示，噪声组豚鼠耳蜗内、外毛细胞均出现听毛紊乱、融合及缺失；而西地那非组耳蜗病变较轻，听毛仅有轻微倒伏、融合现象。结论西地那非能够减轻噪声对豚鼠耳蜗毛细胞的损害，降低噪声性听觉损伤引起的ABR阈值升高。

Objective To investigate the protective effects of sildenafil to noise-induced hearing loss in guinea pigs. Methods Guinea pigs were randomly divided into control group, noise exposure group and the sildenafil treatment group, with 10 in each group. One week after the exposure of 110 dB （A） white noise, sildenafil [ 10 mg/（kg ~ d）] and normal saline [4 ml/（kg· d）3 were injected into guinea pigs of noise plus sildenafil group（NSG） and noise plus normal saline group （NNG） respectively. One week after noise exposure to four weeks continuous administration. ABR thresholds were measured respectively prior to the experiment, 1 week post-noise, 1,2 and 4 weeks post-drugs. The changes of cochlea hair cells were also observed by scanning electron microscope （SEM）. Results After noise exposure, the ABR threshold shifts in NSG were significantly fewer than that in the NNG. An average of 19. 1 dB in NNG compared with 19.8 dB in NSG. Four weeks after exposure, the threshold shifts were become larger to 22.0 dB in NNG while become smaller to 4.8 dB in NSG. Compared NNG with NSG, in addition to noise exposure time point, there were statistically significant differences in the rest time points after administration of the ABR threshold （P 〈 0.05）. SEM showed that the inner and outer hair ceils in NNG displayed mess, fusion and imperfections. In NSG, the hair cells displayed slight pathological changes, there was no significant difference when compared with control group. Conclusion Sildenafil is able to reduce the ascending of ABR thresholds shift, and it can significantly protect against noise-induced hearing loss.