The Role Of AIF In Aspirin Resistance To Gentamicin Ototoxicity

BackgroundThe inner ear hair cells susceptible to ototoxic drug damage, such as aminoglycosideantibiotics. A large number of studies suggest that ototoxic drugs by poptosis induced haircell death. While the Caspase pathway induced hair cell death plays an important role intheototoxic drugs. However, recently the researchers found that drug-induced ototoxic haircell death has not been suppressed by using Caspase inhibitor experiments. AIF played arole in gentamicin-induced deafness in the process. Under normal physiological conditions,AIF is a gap located in the mitochondrial embrane flavoprotein, plays a roleoxidoreductase. When the cells are apoptotic stimuli, AIF uclear translocation occurs,causing chromosome condensation, DNA breakage, leading to apoptosis. In1999-2003our department designed and implemented a multi-center, randomized, double-blindcontrolled study. Research shows that at the same time use of aspirin can reduce gentamicin ototoxicity damage effectively. In the process of spirin against gentamicinototoxicity inwhether AIF functions is not clear. This experiment used the way of ABRand immunofluorescence staining. Observe two groups of hearing and hair cellsmorphological changes in the process of the hair cell apoptosis and the xpression of AIFchanges. In order to study the role of AIF in this experiment that aspirin resistance togentamicin ototoxicity.ObjectiveIn order to study the role of AIF in this experiment that aspirin resistance togentamicin ototoxicity. By making the cochlear damage model of gentamicin, Observedwhen using gentamicin and at the same time use of aspirin audiology changes in rats. Themorphological of cochlear hair cells have changed in two groups. Expression of AIF gotthe same chananged. In order to prove the role of AIF in this experiment that aspirinresistance to gentamicin ototoxicity. For further research on molecular mechanism ofaspirin resistance to gentamicin ototoxicity and discusses the theoretical basis for newtreatment methods.MethodsBy use the model of gentamicin producing aminoglycoside antibioticscochleardamage. Injury group using gentamicin and the protection group using aspirin andgentamicin.1、Through checking the ABR observing two groups rats hearing change.2、Use of cochlear pave piece and immunofluorescence technique, observe two groups haircells morphological changes.3、The cochlear hair cell quantitative analysis system, for2groups of cochlear haircell count.4、Using confocal microscopy to observe the2groups ofAIF nuclear translocation.5、Use RT-PCR and West-blot to detect the expression of thetwo groups basement AIF. By the above method further clarify aspirin resistant ototoxicityprocess and the role of AIF expression. Results1、ASA+GM group of rats after medication7d,14d,21d detection ABR hearing ismuch better than GM group（P<0.05）.2、ASA+GM group rats hair cell loss rate are muchsmaller than GM group.3、ASA+GM group AIF nuclear translocation cases less than theGM group, and the small amount of fluorescence expression.4、RT-PCR and West-blotresults were consistent with the immunofluorescence. In summary, the hearing of rats ASA+GM groups have been protected. To further clarify the exact effect of aspirin resistanceto gentamicin ototoxicity. AIF-mediated apoptosis is also reduced, consistent with theresults of the hearing.ConclusionGentamicin damage cochlear outer hair cells appeared after death, and give priority towith apoptosis and in the expression of AIF nuclear. Expression of AIF in ASA+GM in thenucleus decreased compared with that in GM group. In the process of aspirin againstgentamicin ototoxicity, prevent mitochondrial release of AIF into the nucleus. Reduce theapoptosis of hair cells, to protect the hearing function.