对乙酰氨基酚致小鼠听觉损伤的实验研究

目的：研究对乙酰氨基酚对小鼠听觉的影响。方法：健康7周龄C57小鼠40只，雌雄不分，随机分为4组：对乙酰氨基酚低剂量组（150mg／kg）、中剂量组（300mg／kg）、高剂量组（600mg／kg）及空白对照组（2ml生理盐水）。每组10只。观察每组于喂药第0、2、4、9天ABR反应阈，通过免疫荧光法观测耳蜗基膜毛细胞形态学改变，用高效液相色谱法测定小鼠耳蜗内淋巴液中对乙酰氨基酚浓度。结果：对乙酰氨基酚灌胃30min后，检测小鼠耳蜗内淋巴中对乙酰氨基酚的浓度，内淋巴中药物浓度与灌服剂量相关。对乙酰氨基酚各组随给药时间延长ABR听阈增高，中、高剂量组给药后9d的平均阈值分别为（44．75±16）dB、（50．00±11．00）dB，与对照组比较差异均有统计学意义（均P〈0．05）；随着灌服时间的延长，对乙酰氨基酚各组的免疫荧光镜显示内、外毛细胞出现不同程度的缺失。结论：对乙酰氨基酚可通过血迷路屏障进入内耳，服用一定剂量的对乙酰氨基酚可造成小鼠听力损伤。

Effects of acetamidophenol on auditory in mice

Objective：The purpose of this investigation was to observe the effects of the Acetaminophen on auditory in mice. Method.. Regardless of male and female mice, healthy seven-year-old C57 mice were randomly divided into Aeetaminophen low-dose group （150 mg/kg）, Acetaminophen medium-dose group （300 mg/kg）, Acetaminophen high-dose group（600 mg/kg） and control group. Then mice were tested for ABR to observe the changes of ABR＇s threshold in the zero, second, fourth and ninth day separately. The change of cochlea hair cells morphology was studied by immunofluorescent labeling. And HPLC detects the concentration of Acetaminophen in endolymph of mice cochlea. Result： After 30minutes following administration, the Acetaminophen in endolymph of mice cochlear can be assayed by high performance liquid chromatography （HPLC）. Acetaminophen increased the hearing thresholds compared to the control group. Hearing thresholds increased significantly in the Acetaminophen at 9 d,eompared to the control group （P〈0.05）. After administered medium-dose and high-dose of Acetaminophen,on the 9th day with the time of giving medicine to all the groups strengthens, the ABR thresholds heightens. And the average threshold is （44.75 ±16.00）dB, （50. 00 ± 11.00）dB respectively. Hair cells damages could be observed in experimental group after operations. Conclusion： Acetaminophen can pass through blood-labyrinth barrier to the inner ear. These data demonstrate that taking certain acetaminophen can induce hearing impairment in mice.