Effect Of Autophagy Drug On Zebrafish Hair Cell Damage Induced By Cisplatin And Regeneration After Injury

Objective:In order to look for drugs that can slow down the ototoxicity of cisplatin,we research the effects of autophagy on the protection of injure than cisplatin-induced in zebrafish lateral hair cells and promote the regeneration after hair cells are damaged.Methods:This research used ET4+ET20 transgenic zebrafish,use Rapamycin(mTOR inhibitor,autophagy activator)/ MHY1485(mTOR activator,autophagy inhibitor)and SRT1720(SIRT1 activator,autophagy activator)/ EX527(SIRT1 inhibitor,autophagy inhibitor)to treat the zebrafish after cisplatin injury,and observed the changes of zebrafish lateral hair cells and record the number of hair cells,then evaluate the durgs whether protect zebrafish lateral hair cells which is damaged by cisplatin and the regeneration of hair cells after damaged.Results:The damage of zebrafish hair cells by cisplatin was obvious.The disappearance rate of zebrafish lateral hair cells by rapamycin or SRT1720 together with cisplatin was lower than that use cisplatin alone,and the disappearance rate of MHY1485 or EX527 together with cisplatin were added compareed with exposured in cisplatin.After treatment with cisplatin,rapamycin,MHY1485,SRT1720 and EX527 were used respectively.At the same observation time,the number of hair cell in rapamycin and SRT1720 group is low,and in MHY1485 and EX527 group is numerous.Conclusion:1.Cisplatin has obvioua effects to zebrafish lateral hair cells after damaged by cisplatin;2.Autophagy activator(rapamycin,SRT1720)have no significant damage at low concentrations,high concentration can cause zebrafish hair cell damage even cause zebrafish death;3.Autophagy activator rapamycin and SRT1720 has protective effect on cisplatin-induced damage of zebrafish hair cells;autophagy inhibitors MHY1485 and EX527 will aggravate cisplatin ototoxicity;4.Autophagy activators(rapamycin,SRT1720)have an inhibitory effect to the regeneration of zebrafish hair cells after cisplatin injury,autophagy inhibitor(MHY1485/EX527)have an active effect to the regeneration of zebrafish hair cells after cisplatin injury.