枸橼酸西地那非对小鼠听觉的影响

Effects of sildenafil citrate on mice hearing

目的 探讨枸橼酸西地那非（sildenafil citrate）对小鼠听觉的影响.方法 健康7周龄雄性昆明小鼠按完全随机法分为4组,每组10只,分别为枸橼酸西地那非低剂量组[0.1 mg/（kg·d）]、中剂量组[1 mg/（kg·d）]、高剂量组[10 mg/（kg·d）]以及空白对照组（生理盐水）,每天1次,灌胃给药.分别于给药前、给药后第1、5、10、20天检测各组小鼠的听性脑干反应（ABR）阈值;给药后第20天取材免疫荧光染色观察耳蜗基底膜底回形态学改变.同时利用高效液相色谱法测定一次性给药后小鼠耳蜗内淋巴液中枸橼酸西地那非的浓度.采用SPSS 13.0软件进行统计分析.结果 枸橼酸西地那非灌胃后30 min,小鼠耳蜗内淋巴液中即可检测到西地那非,且药物浓度与灌服剂量相关.西地那非组小鼠随着给药时间的延长,其ABR反应阈有不同程度的升高,其中高剂量组给药后第20天平均阈值为（60.0±10.0）dBnHL,与对照组（14.5±6.0）dBnHL相比,差异具有统计学意义（P＜0.05）.给药20天后,西地那非组小鼠耳蜗底回内、外毛细胞出现不同程度的损伤,剂量越高损伤越重.结论 枸橼酸西地那非可通过口服方式吸收入血并能够通过血迷路屏障进入小鼠内耳;连续服用一定剂量的枸橼酸西地那非可以造成小鼠的听力损伤.

Objective The purpose of this investigation was to study the effects of the Sildenafil citrate on mice hearing.Methods Seven-week-old adult male Kunming mice were used.The mice were randomly divided into four groups with 10 mice in each group.Sildenafil groups were orally administered daily with sildenafil [0.1 mg/（kg · d）,1 mg/（kg · d）,10 mg/（kg · d）] and control group was orally administered with normal saline.Then mice were tested for auditory brainstem response（ABR） to observe the changes of ABR＇s thresholds at before administration and 1,5,10,15,20 day afterwards.The mice basilar membrane samples were studied by immunofluorescent labeling.High performance liquid chromatography was used for determination the concentration of sidenafil in endolymph of mice cochlea.Statistical analysis was performed using SPSS 13.0.Results After 30 min following administration,the Sildenafil in endolymph of mice cochlear could be assayed by high performance liquid chromatography,and it was doserelated.Sildenafil increased the hearing thresholds with the time of administration.Hearing thresholds increased significantly in the sidenafil group at 20 d compared to the control group （P ＜ 0.05）.After administered high dose of Sildenafil,on the 20th day,the ABR thresholds average threshold was （60.0 ± 10.0） dBnHL,and the control group was （14.5 ± 6.0） dBnHL.Hair cells damages in the base ring of cochlea could be observed in experimental group in a concentration-dependent manner.Conclusion Sidenafil can pass through blood-labyrinth barrier to the inner ear,and doses of sildenafil administration can induce hearing impairment in mice.