nhalation of hydrogen gas attenuates ouabainnduced auditory neuropathy in gerbils  

作　　者：Juan QU Yun-na GAN Ke-liang XIE Wen-bo LIU Ya-fei WANG Ren-yi HEI Wen-juan MI Jian-hua QIU 

机构地区：[1]Department of Otolaryngology,Xijing Hospital,Fourth Military Medical University,Xi'an 710032,China [2]Department of Prosthondontics,College of Stomatology,Fourth Military Medical University,Xi'an 710032,China [3]Department of Anesthesiology,General Hospital of Tianjin Medical University,Tianjin 300052,China [4]Department of Neurosurgery,Xijing Institute of Clinical Neuroscience,Xijing Hospital,Fourth Military Medical University,Xi'an 710032,China

出　　处：《Acta Pharmacologica Sinica》2012年第4期445-451,共7页中国药理学报（英文版）

基　　金：Acknowledgements This work was supported by the State Key Program of the National Natural Science Foundation of China （No 30930098 to Jian-hua QIU）, the Major State Basic Research Development Program of China （973 Program） （No 2011CB504505 to Jianhua QIU） and the Young Scientists Fund of the National Natural Science Foundation of China （No 30801287 to Juan QU; 81101409 to Ke-liang XIE）.

摘　　要：Aim： Auditory neuropathy （AN） is a hearing disorder characterized by abnormal auditory nerve function with preservation of normal cochlear hair cells. This study was designed to investigate whether treatment with molecular hydrogen （H2）, which can remedy damage in various organs via reducing oxidative stress, inflammation and apoptosis, is beneficial to ouabain-induced AN in gerbils. Methods： AN model was made by local application of ouabain （1 mmol/L, 20 mL） to the round window membrane in male Mongolian gerbils. H2 treatment was given twice by exposing the animals to H2 （1%, 2%, and 4%） for 60 min at i h and 6 h after ouabain application. Before and 7 d after ouabain application, the hearing status of the animals was evaluated using the auditory brainstem response （ABR） approach, the hear cell function was evaluated with distortion product otoacoustic emissions （DPOAE）. Seven days after ouabain application, the changes in the cochleae, especially the spiral ganglion neurons （SGNs）, were morphologically studied. TUNEL staining and immunofluorescent staining for activated caspase-3 were used to assess the apoptosis of SGNs. Results： Treatment with H2 （2% and 4%） markedly attenuated the click and tone burst-evoked ABR threshold shift at 4, 8, and 16 kHz in ouabainxposed animals. Neither local ouabain application, nor H2 treatment changed the amplitude of DPOAE at 4, 8, and 16 kHz. Morphological study showed that treatment with H2 （2%） significantly alleviated SGN damage and attenuated the loss of SGN density for each turn of cochlea in ouabain-exposed animals. Furthermore, ouabain caused significantly higher numbers of apoptotic SGNs in the cochlea, which was significantly attenuated by the H2 treatment. However, ouabain did not change the morphology of cochlear hair cells. Conclusion： The results demonstrate that H2 treatment is beneficial to ouabain-induced AN via reducing apoptosis. Thus, H2 might be a potential agent for treating hearing impairment in AN patients.Aim： Auditory neuropathy （AN） is a hearing disorder characterized by abnormal auditory nerve function with preservation of normal cochlear hair cells. This study was designed to investigate whether treatment with molecular hydrogen （H2）, which can remedy damage in various organs via reducing oxidative stress, inflammation and apoptosis, is beneficial to ouabain-induced AN in gerbils. Methods： AN model was made by local application of ouabain （1 mmol/L, 20 mL） to the round window membrane in male Mongolian gerbils. H2 treatment was given twice by exposing the animals to H2 （1%, 2%, and 4%） for 60 min at i h and 6 h after ouabain application. Before and 7 d after ouabain application, the hearing status of the animals was evaluated using the auditory brainstem response （ABR） approach, the hear cell function was evaluated with distortion product otoacoustic emissions （DPOAE）. Seven days after ouabain application, the changes in the cochleae, especially the spiral ganglion neurons （SGNs）, were morphologically studied. TUNEL staining and immunofluorescent staining for activated caspase-3 were used to assess the apoptosis of SGNs. Results： Treatment with H2 （2% and 4%） markedly attenuated the click and tone burst-evoked ABR threshold shift at 4, 8, and 16 kHz in ouabainxposed animals. Neither local ouabain application, nor H2 treatment changed the amplitude of DPOAE at 4, 8, and 16 kHz. Morphological study showed that treatment with H2 （2%） significantly alleviated SGN damage and attenuated the loss of SGN density for each turn of cochlea in ouabain-exposed animals. Furthermore, ouabain caused significantly higher numbers of apoptotic SGNs in the cochlea, which was significantly attenuated by the H2 treatment. However, ouabain did not change the morphology of cochlear hair cells. Conclusion： The results demonstrate that H2 treatment is beneficial to ouabain-induced AN via reducing apoptosis. Thus, H2 might be a potential agent for treating hearing impairment in AN patients.

关 键 词：auditory neuropathy （AN） OUABAIN hearing loss hydrogen gas （H2） COCHLEA spiral ganglion neuron hair cell auditory brainstem response distortion product otoacoustic emissions apoptosis 

分 类 号：Q959.837[生物学—动物学] D918.9[政治法律—法学]