Protective Role Of Hydrogen Sulfide Against Noise-induced Cochlear Damage

Objective:Reduction of cochlear blood flow plays an essential role in noise-induced hearing loss (NIHL). Therefore, timely regulation of cochlear perfusion determines the progression and prognosis of NIHL. Hydrogen sulfide (H2S) attracts increasing interest as a vasodilator in cardiovascular system recently. However, there are few studies about it in cochlea. Cochlear expressions of cystathionine-γ-lyase (CSE) protein and mRNA have been verified by immunostaining and reverse transcriptase polymerase chain reaction (RT-PCR). In this study, we aim to explore the regulatory effect of H2S on cochlear blood flow, and then identify the protective role of H2S against NIHL in order to provide a new preventive and therapeutic perspective for blood supply-related inner ear diseases.Methods:First, a chronic intracochlear infusion model was built to administer artificial perilymph (AP), sodium hydrosulfide (NaHS) or DL-propargylglycine (PPG) locally and persistently. Then conventional auditory brainstem response (ABR) measurement, cochlear scanning electron microscope (SEM) and outer hair cell (OHC) count were carried out and results were compared among the three groups.Second, by administration via the scala tympani, cochlear blood flow was detected to explore the contribution of noise and exogenous H2S to cochlear perfusion.Next, direct effect of NaHS on capillary was explored by a multi wire myograph system.Results:By preventive administration of NaHS via scala tympani, ABR threshold shifts of animal was decreased significantly than those of PPG group, which suggests the protective effect of H2S on audition. By cochlear sensory epithelia surface preparation and outer hair cell count, we found that there was a statistically less missing rate in NaHS group than the other two groups. Besides, the morphologic damage was less significantly. There was the highest missing rate in PPG group. By scanning electron microscope, the least damage was observed in NaHS group. Obvious loss of hair cell and lodging of stereocilium were found in PPG and control group. These results show that H2S could protect cochlea against noise effectively.After short-time noise stimulation, a obvious decrease of cochlear perfusion could be found by laser-Doppler and laser speckle blood flow imager. After NaHS administration via the round window, cochlear blood flow increased obviously. Those mean that H2S could increase cochlear perfusion and counteract against noise-induced perfusion disorder.When the final concentration of NaHS reached 30mmol/L, a vasodilator effect was detected by DMT multi wire myograph system. Although the effect was momentary, a dose-effect action was observed. After destroy of vascular endothelium, the vasodilator effect also exist. These results suggest that H2S act directly on vascular smooth muscle cell to take the vasodilator effect. Conclusion:Exogenous H2S can protect cochlea against noise-induced damage. This effect may result from the release of noise-induced cochlear blood disorder, which results from the vasodilator and perfusion-increased effect of H2S. We demonstrate for the first time that H2S play an important role in regulation of cochlear blood flow. Further studies will shed more light on prevention and therapy of noise-induced hearing loss and other blood supply-related inner ear diseases.