西地那非对噪声性聋豚鼠耳蜗外毛细胞及听功能的影响

The Effect of the PDE5 Inhibitor on Noise-induced Hearing Loss

目的探讨5-磷酸二酯酶(phosphodiesterasetype 5,PDE5)抑制剂西地那非对噪声性聋豚鼠耳蜗显微结构的影响。方法 30只豚鼠随机分为对照组、噪声暴露组和PDE5抑制剂组,每组10只。PDE5抑制剂组和噪声暴露组豚鼠在110dB SPL白噪声暴露2周后分别腹腔注射西地那非10mg·kg-1·d-1及生理盐水4ml·kg-1·d-1,连续给药4周;对照组安静环境饲养,不给予噪声暴露及任何药物。分别于噪声暴露前1天、噪声暴露后给药前及给药第1、2及4周各组行ABR检测,并通过光镜观察噪声暴露后4周豚鼠耳蜗外毛细胞缺失率变化。结果与噪声暴露前相比,PDE5抑制剂组和噪声暴露组ABR反应阈明显升高,波I潜伏期明显延长,但PDE5抑制剂组的增幅均小于噪声暴露组,差异有统计学意义(P<0.01)。正常对照组外毛细胞无明显缺失,噪声暴露组和PDE5抑制组外毛细胞缺失率分别为39.30%±5.69%和37.13%±7.81%,两组间差异无统计学意义(P>0.05)。结论 PDE5抑制剂不能促使坏死脱落的毛细胞再生,但能在一定程度上恢复噪声性听力损失豚鼠的听功能。

Objective To study the effect of the PDE5 inhibitor on noise-induced hearing loss.Methods 30 guinea pigs were randomly divided into control group,noise exposure group and PDE5 inbibiter group（10in each）.Two weeks after white noise exposure of 110 dB,sildenafil（10mg·kg^-1·d^-1）and NS（4ml·kg^-1·d^-1）were injected into guinea pigs of PDE5 inbibiter group and the noise group respectively.One week after noise exposure four weeks continuous administration was cavried out.The ABR thresholds and the PL of waveⅠ were measured respectively prior to the experiment,1week post-noise,1,2and 4weeks post-drugs.The changes of cochlea hair cells were also observed by light microscopy.Results The ABR threshold shifts and the PL in sildenafil group were less obvious than that of in the noise group.The number of OHCs loss was relatively stable in the normal group,while the obvious OHC loss was observed in other groups.There was significant difference among the three groups,however,the OHC loss in the sildenafil treatment group was not significantly different from that in the noise exposure（P〉0.05）.Conclusion The inhibitor of PDE5 is able to reduce the decrease of ABR thresholds shift,shorten the extension of the PL,and it can significantly protect against noise-induced hearing loss.