Objective:To explore the protective effect of α-lipoic acid (LA) on radiation damage of mice cochlear ribbon synapses.Methods:Mice were divided into five groups: control group, radiation 3 d group, radiation 3 d+ LA group, radiation 14 d group and radiation 14 d+ LA group. The radiation groups were irradiated with 16 Gy, the radiation+ LA groups were given LA once a day after radiation, the control group was given the same amount of normal saline. The auditory brainstem response (ABR) of mice were measured before irradiation and sacrifice. The number of ribbon synapses were observed with immunofluorescently labeled protein ctBP2. Western blot assay was performed to obtain the semi-quantitative expression levels of otoferlin and AP-2 protein.Results:Compared with the control group, the ABR threshold of radiation groups were significantly higher ( P<0.05) with the highest value at 14 d after irradiation ( P<0.05), and the ABR threshold of the radiation+ LA groups were significantly lower ( P<0.05). The ABR threshold shifts of 12 kHz, 24 kHz at 3 d and 14 d groups had no significant difference with 8 kHz threshold shift ( P>0.05). The 32 kHz threshold shift was significantly higher than 8 kHz threshold shift ( t=-2.38, -5.48, P<0.05). The number of ribbon synapses in the radiation groups was significantly lower than that of control group ( P<0.05), with the lowest value in the radiation 14 d group. LA treatment increased the ABR value significantly ( P<0.05). AP-2 and otoferlin protein levels were significantly reduced after irradiation, especially in the radiation 14 d groups, and they were increased by the LA treatment. Conclusions:LA has protective effect on the ribbon synapses of cochlear hair cells.