The Study On The Protective Effects And Mechanism Of Fasudil On The Injury Of The HEI-OC1 Induced By Neomycin

Deafness hold the hignest incidence in the world in sensory-organ disabling diseases,which are divided into conductive hearing loss and sensorineural hearing loss.Aminoglycoside antibiotics are the most common ototoxic drugs.And neomycin is the representative drug.The damage of inner ear hair cells caused by aminoglycoside antibiotics can lead to sensorineural hearing loss,which is one of the main causes of drug-induced deafness.How to prevent hair cell injury and protect hearing function is a key scientific problem.Aminoglycoside antibiotics have mainly effect on gram-negative bacilli.Although their price is low,they are effective in the treatment of severe gram-negative bacilli.So they are widely used in clinical practice.Therefore,at the same time of the choice of such drugs to save lives,severe gram-negative bacteria infection in patients with hearing caused the different degrees of damage.Even some of them got complete deafness.But ototoxic side effects can lead to permanent sensorineural hearing loss or loss of vestibular function.It has been found that aminoglycoside drugs can cause the death of hair cells in the inner ear,and the possible mechanisms are autophagy,apoptosis,necrosis and so on.Aminoglycoside antibiotics mainly act on the mitochondria and lysosomes in the hair cells of the inner ear,resulting in increased generation of oxygen free radicals in the cells and further apoptosis of the hair cells of the inner ear.Therefore,topical or systemic application of oxygen free radical scavengers or oxygen free radical inhibitors may protect the inner ear hair cells from the damage caused by aminoglycoside antibiotics.So far,there is no effective drug treatment for drug-induced deafness.In our preliminary experiments,fasudil has obvious protective effects on the HEI-OC1 damaged by neomycin.Therefore,on the basis of the damage of HEI-OC1 cells caused by neomycin,this paper studies the protective effect of fasudil on sensorinear hearing loss caused by aminoglycoside antibiotics and its molecular mechanism.The research contents were as follows.Firstly,the concentration of fasudil on hair cell injury was studied in the model of neomycin injury in HEI-OC1 cells.Secondly,In the cell damage model of HEI-OC1 induced by neomycin,the protective effect of fasudil on HEI-OC1 cell damage was explored.Lastly,to study the molecular mechanism of fasudil's protective effect on the damage of the HEI-OC1 cell caused by neomycin.The results showed that fasudil had a protective effect on HEI-OC1 cell damage induced by neomycin at appropriate concentration.The molecular mechanism may be by inhibiting the production of oxygen radicals and/or inhibiting the relevant factors of the Rho/JNK signaling pathway.This paper provides theoretical and experimental basis for clinical prevention and treatment of drug-induced deafness caused by aminoglycoside antibiotics.