1、书书书doi:1011659/jjssx10E022001基础研究急入高海拔环境后对听觉的影响研究邹文进1，柯静2，周小清2，胡蜜2，袁伟2(1 陆军军医大学第一附属医院耳鼻咽喉头颈外科，重庆 400038;2 重庆市人民医院耳鼻咽喉头颈外科，重庆 400112)摘要 目的通过模拟高海拔环境对急进入高原人群听力的变化进行研究，并建立动物模型研究急进高原对听觉系统的影响，为急性缺氧引起的耳聋治疗提供理论依据。方法选择拟急进入高原的受试者，在进入高原前，受试者进入模拟海拔 5 000 m的低压氧舱内适应 5 h，在入舱前后进行纯音测听(测试频率为 250 Hz、500 Hz、1 kHz、2 kHz
2、、4 kHz、8 kHz)。比较受试者入舱前后纯音测听的结果，并进行统计学分析。根据此结果建立动物模型，选取健康雄性 C57 小鼠 50 只，将小鼠随机分为对照组、缺氧 5 h组、缺氧 10 h 组、缺氧 24 h 组、缺氧 48 h 组，每组 10 只。低压低氧动物实验舱模拟海拔 5 000 m 高原环境，采用听觉脑干诱发电位(AB)测量小鼠听力变化情况。结果受试者入舱后听力较入舱前有一定变化，双耳听阈及大多数频率(250 Hz、500 Hz、1 kHz、8 kHz)的纯音测听阈值较入舱前升高，差异有统计学意义(P 005)，右耳中频(2 kHz)纯音测听阈值较入舱前无显著变化(P 0 05
3、)。在动物实验中，实验组、波潜伏期较对照组延长(P 0 05)，波的潜伏期在缺氧 5 h、10 h 与对照组有明显差异(P 0 05)，缺氧24 h、48 h 与对照组差异无统计学意义(P=0 050)。各组 click 幅值及纯音测听阈值变化比较，差异均无统计学意义(P 0 05)。结论模拟高海拔环境对急进入高原人群的听力存在一定程度的影响，可能和急进高原导致的急性缺氧有关，应给予高度重视，并采取相应措施积极预防。关键词急性高原病;听力;缺氧;耳蜗 中图分类号764 4 文献标识码A 收稿日期2022-10-02 基金项目国家自然科学基金项目(81873702);教育部极端环境医学重点实验室
4、开放课题(KL2019GY002);重庆市人民医院医学科技创新基金(Y2020ZDXM01);重庆市卫健委重大项目(2022DBXM006)通信作者袁伟，E-mail:weiyuan175 sina comEffect of sudden entry into high altitude environment on hearingZOU Wen-jin1，KE Jing2，ZHOU Xiao-qing2，HU Mi2，YUAN Wei2(1 Department of Otolaryngology Head and Neck Surgery，First Affiliated Hospital
5、 of Army Medical University，Chongqing 400038，China;2 Department of Otolaryngology Head and Neck Surgery，Chongqing General Hospital，Chongqing 400112，China)Abstract:ObjectiveTo study the changes of hearing of people who suddenly entered into the plateau by simulating high altitude environ-ment，and est
6、ablish animal models to study the effect of sudden entry into the plateau on auditory system，aiming at providing a theoreticalbasis for the treatment of deafness caused by acute hypoxia MethodsThe subjects who intended to suddenly enter into the plateau wereselected Before entering the plateau，the s
7、ubjects entered the low-pressure oxygen chamber with a simulated altitude of 5 000 meters to adaptfor 5 hours Pure tone audiometry(the test frequencies were 250 Hz，500 Hz，1 kHz，2 kHz，4 kHz，8 kHz)was performed before and afterentering the chamber The results of pure tone audiometry before and after t
8、he subjects entered the chamber were compared and statisticallyanalyzed According to the results，the animal models were established A total of 50 healthy C57 male mice were selected and randomlydivided into the control group，the hypoxia group for 5 hours，the hypoxia group for 10 hours，the hypoxia gr
9、oup for 24 hours，and the hypoxiagroup for 48 hours，with 10 mice in each group The plateau environment at altitude of 5 000 meters was simulated by the low-pressure oxygenanimal experimental chamber，and the hearing changes of mice were measured by the auditory brainstem response(AB)esultsAfterenterin
10、g the chamber，the hearing of subjects changed to a certain extent compared with that before entering the chamber The binaural hearingthresholds and the pure tone audiometry thresholds of most frequencies(250 Hz，500 Hz，1 kHz，and 8 kHz)were higher than those beforeentering the chamber，and the differen
11、ces were statistically significant(P 0 05)The pure tone audiometry threshold of intermediatefrequency(2 kHz)in the right ear had no significant change compared with that before entering the chamber(P 005)In animal experiments，the latencies of waves，and in the experimental groups were longer than tho
12、se in the control group(P 0 05)，and the latenciesof wave V at 5 hours and 10 hours after hypoxia were significantly different from that of the control group(P 0 05)，and those at 24 hoursand 48 hours after hyposia were not significantly different from that in the control group(P=0 050)There was no st
13、atistically significantdifference in the click amplitude or pure tone audiometry threshold among all groups(P 0 05)ConclusionThe simulated high altitude781局解手术学杂志J EG ANAT OPE SUG2023，32(3)http:/www jjssxzz cnenvironment has a certain degree of effect on the hearing of people who suddenly enter into
14、 the plateau，which may be related to the acutehypoxia caused by sudden entry into the plateau Therefore，we should pay great attention to it and take corresponding preventive measuresKeywords:acute mountain sickness;hearing;hypoxia;cochlea随着交通条件好转，越来越多的人群开始从平原地区急入高原地区经商、旅游，随之而来的急性高原病也逐渐增加。高原由于其环境的特殊性
15、，对机体的影响是全身性的，一直以来对于高原病的研究较多关注心、脑、肾等器官功能的损伤，而对听力是否有影响目前尚不清楚。有研究表明，随着海拔增加，大气压逐渐下降，氧含量逐渐降低，海拔 3 000 m 氧含量减少30%，海拔5 500 m 氧含量减少50%1，因此造就了高原缺氧环境。急性高原反应是指由平原快速进入海拔3 000 m 以上的高原，或由高原进入海拔更高的地区，在数小时或3 d 内发病，经3 10 d 的适应后症状可逐渐消失。绝大多数急性高原反应与急性缺氧有关，耳蜗及听觉中枢对缺氧极为敏感，既往有研究证实长期缺氧可导致听力下降2-6。急进高原所致的急性缺氧是否会损伤听力值得深入探讨。研究
16、表明，男性听力损失发生率高于女性2，7-9，本研究招募了 65 例即将进入高原地区的青年男性受试者，对其进行高原预缺氧训练，即进入模拟高原缺氧的低压氧舱适应来探讨高原急性缺氧对听力的影响。同时进行动物实验进一步验证，现报告如下。1资料与方法1 1临床资料招募 2020 年 12 月 2 日至 2020 年 12 月 6 日即将进入高原地区的健康青年男性受试者，在低压氧舱内进行预缺氧适应。最终纳入 65 例男性受试者，年龄18 25 岁，本研究经陆军军医大学伦理委员会审批通过(2020 第 003-03)，所有受试者均签署知情同意书。纳入标准:既往无耳科相关疾病，入舱前测试听力正常。排除标准:有脑血管事件、颅脑外伤、桥小脑角肿瘤、鼻咽癌等严重疾病;高血压、糖尿病、肝肾功能不全，有激素禁忌;中耳炎、美尼尔病、流行性腮腺炎、Hunt 综合征。氧舱标准:低压氧舱模拟海拔 5 000 m 高原环境，上升速度 2 7 m/s，大气压 54 047 kPa，氧浓度 10%11%，舱内温度 18 23。1 2方法受试者进入模拟海拔 5 000 m 的低压氧舱内适应5 h，期间受试者的平均氧饱和度为 7