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

doi:10.13481/j.1671-587X.20220405

Abstract

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

CLC Number:

R363.16

Shuyuan YU,Ping WANG,Xinrui WANG,Lanzi GONGGA,Li YANG. Effects of high altitude hypoxia on auditory conduction and peripheral auditory nerve myelin regeneration in plateau migrated rats[J].Journal of Jilin University(Medicine Edition), 2022, 48(4): 875-882.

Figures/Tables 7

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References 25

1	FRISANCHO A R. Developmental functional adaptation to high altitude： review［J］. Am J Hum Biol， 2013， 25（2）： 151-168.
2	JI W Z， ZHANG Y Q， GE R L， et al. NMDA receptor-mediated excitotoxicity is involved in neuronal apoptosis and cognitive impairment induced by chronic hypobaric hypoxia exposure at high altitude［J］. High Alt Med Biol， 2021， 22（1）： 45-57.
3	DAVIS C， HACKETT P. Advances in the prevention and treatment of high altitude illness［J］. Emerg Med Clin North Am， 2017， 35（2）： 241-260.
4	任海龙，潘永越，高道光，等. 高原环境对听力健康影响的调查研究［J］. 西藏医药， 2015， 36（2）： 4-6.
5	WANG P， DU B， YIN W Z， et al. Resveratrol attenuates CoCl₂-induced cochlear hair cell damage through upregulation of Sirtuin1 and NF-κB deacetylation［J］. PLoS One， 2013， 8（11）： e80854.
6	WUREN T N， NORYUNG T， BURTON G J， et al. Protective effects from the ischemic/hypoxic stress induced by labor in the high-altitude Tibetan placenta［J］. Reprod Sci， 2021， 28（3）： 659-664.
7	JOZEFCZUK J， ADJAYE J. Quantitative real-time PCR-based analysis of gene expression［J］. Methods Enzymol， 2011， 500： 99-109.
8	LIN J C， HUANG H， LV G R， et al. Chronic prenatal hypoxia impairs cochlear development， a mechanism involving connexin26 expression and promoter methylation［J］. Int J Mol Med， 2018， 41（2）： 852-858.
9	LI X， CHEN W J， ZHANG X Y， et al. Inner ear function in patients with obstructive sleep apnea［J］. Schlaf Atmung， 2020， 24（1）： 65-69.
10	KAYABASI S， HIZLI O， YILDIRIM G. The association between obstructive sleep apnea and hearing loss： a cross-sectional analysis［J］. Eur Arch Otorhinolaryngol， 2019， 276（8）： 2215-2221.
11	JULIAN C G. Epigenomics and human adaptation to high altitude［J］. J Appl Physiol （1985）， 2017， 123（5）： 1362-1370.
12	IDE R， HARADA T， KANZAKI S， et al. Physical and physiological effects on otoacoustic emissions in hypobaric hypoxia［J］. ORL J Otorhinolaryngol Relat Spec， 2010， 72（4）： 225-232.
13	COUNTER S A， BUCHANAN L H， ORTEGA F. Brainstem auditory evoked responses in children living at high altitude in the Andes mountains［J］. High Alt Med Biol， 2013， 14（2）： 155-161.
14	SINGH S B， THAKUR L， ANAND J P， et al. Effect of high altitude on human auditory brainstem responses［J］. Indian J Physiol Pharmacol，2004，48（2）： 230-234.
15	CHEN T J， CHEN S S. Generator study of brainstem auditory evoked potentials by a radiofrequency lesion method in rats［J］. Exp Brain Res，1991，85（3）： 537-542.
16	王艳萍，朱贺，马克涛，等.急性缺氧对SD乳鼠耳蜗螺旋神经节细胞钾通道的影响［J］.中华耳鼻咽喉头颈外科杂志， 2015，50（10）： 823-828.
17	CEPRIÁN M， VARGAS C， GARCÍA-TOSCANO L， et al. Cannabidiol administration prevents hypoxia-ischemia-induced hypomyelination in newborn rats［J］. Front Pharmacol， 2019， 10： 1131.
18	CUI Y X， JIN X L， CHOI D J， et al. Axonal degeneration in an in vitro model of ischemic white matter injury［J］. Neurobiol Dis， 2020， 134： 104672.
19	WANG F， YANG Y J， YANG N， et al. Enhancing oligodendrocyte myelination rescues synaptic loss and improves functional recovery after chronic hypoxia［J］. Neuron， 2018， 99（4）： 689-701.e5.
20	KAWASAKI A， OKADA M， TAMADA A， et al. Growth cone phosphoproteomics reveals that GAP-43 phosphorylated by JNK is a marker of axon growth and regeneration［J］. iScience， 2018， 4： 190-203.
21	NI Y S， CHEN D Y， JIANG Y， et al. The regenerative potential of facial nerve motoneurons following chronic axotomy in rats［J］. Neural Plast， 2020， 2020： 8884511.
22	LI L X， LI Y Y， FAN Z H， et al. Ascorbic acid facilitates neural regeneration after sciatic nerve crush injury［J］. Front Cell Neurosci， 2019， 13： 108.
23	BENOWITZ L I， ROUTTENBERG A. GAP-43： an intrinsic determinant of neuronal development and plasticity［J］. Trends Neurosci， 1997， 20（2）： 84-91.
24	MERINO P， DIAZ A， TORRE E R， et al. Urokinase-type plasminogen activator （uPA） regulates the expression and function of growth-associated protein 43 （GAP-43） in the synapse［J］.J Biol Chem， 2020，295（2）： 619-630.
25	CHEN H C， SYTWU H K， CHANG J L， et al. Hypoxia enhances the stemness markers of cochlear stem/progenitor cells and expands sphere formation through activation of hypoxia-inducible factor-1 alpha［J］. Hear Res， 2011， 275（1/2）： 43-52.

Group	ABR （dB SPL）	Peak latency(t/ms)
Group	ABR （dB SPL）	Ⅰ	Ⅲ
Control	25.6±4.78	1.43±0.15	3.54±0.11
Migration plateau
2 months	36.6±6.73	1.68±0.21^*	3.88±0.32^*
4 months	38.7±7.53	1.59±0.13^*	3.76±0.27^*
10 months	30.4±6.43	1.50±0.25	3.69±0.25

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

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