吉林大学学报(医学版) ›› 2022, Vol. 48 ›› Issue (4): 875-882.doi: 10.13481/j.1671-587X.20220405

• 基础研究 • 上一篇    下一篇

高原缺氧环境对平原移居大鼠听觉传导和外周听神经髓鞘再生的影响

于姝媛1,王苹1,王心蕊2,龚嘎蓝孜3,杨丽2()   

  1. 1.吉林大学第一医院耳鼻咽喉-头颈外科,吉林 长春 130021
    2.吉林大学动物医学学院教育部人兽共患病研究所,吉林 长春 130062
    3.西藏大学医学院预防医学系,西藏 拉萨 850000
  • 收稿日期:2021-10-09 出版日期:2022-07-28 发布日期:2022-07-26
  • 通讯作者: 杨丽 E-mail:ccyangli@jlu.edu.cn
  • 作者简介:于姝媛(1986-),女,吉林省东丰县人,技师,药学学士,主要从事耳科学基础方面的研究。
  • 基金资助:
    国家自然科学基金项目(81860567);吉林省科技厅自然科学基金项目(20200201493JC)

Effects of high altitude hypoxia on auditory conduction and peripheral auditory nerve myelin regeneration in plateau migrated rats

Shuyuan YU1,Ping WANG1,Xinrui WANG2,Lanzi GONGGA3,Li YANG2()   

  1. 1.Department of Otolaryngology and Head-Neck Surgery,First Hospital,Jilin University,Changchun 130021,China
    2.Institute of Zoonoses,Ministry of Education,College of Zoology,Jilin University,Changchun 130062,China
    3.Department of Preventive Medicine,School of Medical Sciences,Tibet University,Tibet 850000,China
  • Received:2021-10-09 Online:2022-07-28 Published:2022-07-26
  • Contact: Li YANG E-mail:ccyangli@jlu.edu.cn

摘要: 目的

探讨高原缺氧环境对平原移居大鼠听力的影响,阐明大鼠听觉系统适应缺氧产生听习服的分子机制。

方法

72只Wistar 大鼠随机分为对照组(平原对照)、移居高原2月组、移居高原4月组和移居高原10月组,每组18只。分别在移居高原2、4和10个月时间点检测各组大鼠听觉脑干诱发电位(ABR)阈值和潜伏期,采用透射电子显微镜观察各组大鼠耳蜗组织中神经元和神经纤维髓鞘超微结构,采用实时荧光定量PCR(RT-qPCR)法、Western Blotting法和免疫组织化学染色检测各组大鼠耳蜗组织中生长相关蛋白43(GAP-43)和髓鞘碱性蛋白(MBP)mRNA和蛋白表达水平。

结果

与对照组比较,移居高原各组大鼠ABR阈值增高5~13 dB,但差异均无统计学意义(P>0.05)。 在声强度为80 dB SPL的Click声刺激下测定大鼠ABR各波潜伏期,与对照组比较,移居高原2和4月组大鼠Ⅰ波和Ⅲ波潜伏期明显延长(P<0.05)。透射电镜观察,对照组大鼠耳蜗听神经髓鞘结构完整,板层排列紧密有序;移居高原2月组大鼠出现严重的耳蜗听神经髓鞘板层分离,神经元包绕的髓鞘出现断裂,细胞与髓鞘间隙增大,细胞内线粒体结构异常;移居高原4月组大鼠耳蜗听神经髓鞘病变减轻;移居高原10月组大鼠耳蜗听神经髓鞘结构与对照组比较无明显差异。RT-qPCR、Western blotting和免疫组织化学染色法检测,与对照组比较,移居高原2和4月组大鼠耳蜗组织中MBP mRNA及蛋白表达水平明显降低(P<0.01),移居高原10月组大鼠耳蜗组织中MBP和GAP-43 mRNA及蛋白表达水平差异无统计学意义(P>0.05);与对照组比较,移居高原2月组大鼠耳蜗组织中GAP-43 mRNA和蛋白表达水平明显降低(P<0.01);与移居高原2月组比较,移居高原4月组大鼠耳蜗组织中GAP-43 mRNA和蛋白表达水平明显升高(P<0.05)。

结论

高原低氧环境可引起外周听神经髓鞘损伤,导致ABR潜伏期延长,影响听觉信号传导。长期低氧环境可诱导听神经髓鞘再生,产生听觉适应性修复。

关键词: 听神经, 髓鞘, 缺氧, 适应性, 高原环境, 信号传导

Abstract: Objective

To explore the effects of altitude anoxic environment on the hearing of rats that migrated from the plain to the plateau,and to elucidate the molecular mechanism of sound acclimation in the rats.

Methods

A total of 72 Wistar rats were divided into plain control group,migration plateau 2 months group,migration plateau 4 months group and migration plateau 10 months group,with 18 rats in each group. The auditory brainstem response evoked by click(ABR)thresholds and latencies of the rats were detected at 2, 4 and 10 months after migration to the plateau. The ultrastructures of neurons and myelin sheath in cochlear tissue of the rats were observed by transmission electron microscope. The expression levels of growth associated protein-43(GAP-43)and myelin basic protein (MBP) mRNA and proteins in cochlear tissue of the rats in various groups were analyzed by real-time fluorescence quantitative PCR (RT-qPCR) method,Western blotting method and immunohistochemistry method.

Results

Compared with control group, the thresholds of ABR of the rats in migration plateau groups were increased for 5-13 dB, but there were no statistical differences(P>0.05). The lantencies of ABR of rats were detected after stimulated with Crik of 80 dB SPL;compared with control group,the lantencies of wave Ⅰ and Ⅲ of the rats in migration plateau 2 months group and migration plateau 4 months group were prolonged(P<0.05).The transmission electron microscope results showed that myelin sheath structure appeared intact and lamellar arrangement was close and orderly in control group; the most serious myelin injury occurred at the time of 2 months after the migration to the plateau, appeared the lamellar arrangement separated, the myelin sheaths around neurons were broken, and the space between cells and myelin sheaths was increased; meanwhile, the abnormal mitochondrial structure was also found. At the time of 4 months after the migration to the plateau, the myelin lesion was relieved, and at the time of 10 months, the myelin structure was almost normal. The results of RT-qPCR and Western blotting methods showed that compared with control group, the expression levels of MBP mRNA and protein in cochlear tissue of the rats in migration plateau 2 months group and migration 4 months group were decreased(P<0.01);but the expression levels of MBP and GAP-43 mRNA and protein in cochlear tissue of the rats in migration plateau 10 months group had no significant differences(P>0.05).Compared with control group,the expression levels of GAP-43 mRNA and protein in cochlear tissue of the rats in migration plateau 2 months group were decreased(P<0.01). Compared with plateau migration 2 months group, the expression levels of GAP-43 mRNA and protein in cochlear tissue of the rats in migration plateau 4 months group were increased(P<0.05).

Conclusion

High altitude hypoxic environment can cause the peripheral auditory nerve myelin injury, lead to the prolonged ABR latency and affect the auditory signal transduction. Long-term hypoxic environment can induce myelin sheath regeneration and induce auditory adaptive repair.

Key words: Auditory nerve, Myelination, Hypoxia, Adaptation, Altitude environment, Signal transduction

中图分类号: 

  • R363.16