Noise Induced Change Of Metalloproteinases In Cochlea And Affect To Audiologic Function

Noise is the most common factors of occupational injury and hearing disability.Therefore, how to prevent the happening of NIHL and reduce the extent of hearing lossis one of the important subjects that we otology scholars hammer away at. Formerresearches show the damage caused by noise is multiple factors, which include cochleamechanical damage, blood flow reduction following the change of cochlearmicroenvironment, hair cells loss and the malfunction of blood labyrinth barrier causedby metabolism disorder, etc. In this topic, we study noise induced change of reactivenitrogen free radicals and metalloproteinases in cochlea and affect to audiologicfunction. The results are as follows:1. Noise induced change of reactive nitrogen free radicals in cochlea and affect toaudiologic functionNO rapidly oxidized to peroxynitrite (ONOO-) can mediate cell pathological reaction.ONOO-is one of the most active and toxic nitrogen free radicals, which plays the roleby nitrated tyrosine and its residues.3-nitrotyrosine (3-NT) is a product in the process,which can be used as a marker to detect reactive nitrogen free radicals. In the process ofthis experiment, we established the noise deafness model with120dBSPL white noisesuccessfully. Through auditory brainstem response, distortion product otoacousticemission, electric auditory brainstem response to evaluate the degree of hearing loss, wefound the ABR threshold, eABR amplitude increased obviously after noise exposure,DPOAE amplitude declined significantly. It shows the outer hair cells and auditorynerve have damage after120dBSPL white noise exposure. Then using the cochlearsurface preparation, temporal bone frozen section, immunohistochemistry, confocallaser scanning microscopy, we found there is RNS in the cochlea under normalcircumstances. In the outer hair cells, it is mainly distributed in the cytoplasm and the epidermis plate, but rarely in nuclei or its surrounding. And it is also distributed in thestria vascularis of the lateral wall and spiral ganglion cell. The fluorescence of ONOO-marker obviously enhanced in noise exposure group. Through Western blot, we furthervalidate the RNS content increase within the cochlea after noise exposure.2. Noise induced change of metalloproteinases in cochlea and affect to audiologicfunctionSome studies indicate that ONOO–is able to activate the matrix metalloproteinases(MMPs) in cerebral ischemia injury, and further degrade the tight junction proteins onthe cerebrovascular basement membrane, eventually break the blood-brain barrier(BBB). Blood labyrinth barrier(BLB) is also the human barrier system as the BBB.MMP-2and MMP-9which are the principle members of MMPs family in the cochleaare the only proteolytic enzymes that can degrade the extracellular matrix. Normal levelof MMPs is beneficial. But it is harmful when MMPs significantly increases after theinjury. Theoretically, MMPs which may be activated by cochlear injury can increase thepermeability of blood labyrinth barrier, change the K+concentration and disrupt theendolymph homeostasis, eventually cause sensorineural deafness. In the process of thisexperiment, we used almose the same techniques and found there was MMPs in thecochlea under normal circumstances. MMP-9is mainly distributed in stria vascularis,and MMP-2in basement membrane; MMP-9and MMP-2obviously enhanced in noiseexposure group. It may degrade extracellular matrix of the stria vascularis and basementmembrane, and cause disorder of internal environment.This study explore molecular biology mechanism of NIHL on the cellular andsubcellular level preliminary. It shows that noise exposure can lead to the increase ofRNS and MMPs in the cochlea. And the audiologic functions have a significant affect.From the cellular and molecular mechanisms of NIHL, it may open up a new way forthe prevention and treatment to this problem.