To investigate the protective effect of astragaloside IV (ASIV) against nerve injury caused by high doses of S-ketamine (SK),PC12 cells were used to construct an in vitro nerve injury model.The cell viability was measured by CCK-8 method,from which the optimal modeling concentration for SK and the optimal therapeutic concentration for ASIV were determined.Flow cytometry was used to determine the apoptosis rate.Reactive oxygen species (ROS) was detected by DCFH-DA fluorescent probe assay.Expressions of the target genes were measured by qPCR and the target proteins were detected by Western blot.The results showed that the optimal modeling concentration for SK was 450 μg/mL and the optimal therapeutic concentration for ASIV was 25 μmol/L.Compared with the control group,the apoptosis rate,ROS content,Caspase-9 and Cytochrome C mRNA expression levels were significantly increased in the SK group (P < 0.05).On the other hand,Bax,Pro-Caspase-9,Cleaved-Caspase-9 and Cytochrome C protein expression levels were similarly markedly increased (P< 0.05),while the ratio of Bcl-2/Bax mRNA expression levels and Bcl-2 protein expression level were significantly decreased (P< 0.05).After treatment with ASIV,the changes in all indices induced by high-dose SK were clearly reversed (P< 0.05).Therefore,ASIV attenuates PC12 cell injury caused by high dose of SK through a mechanism that may be related to inhibition of the mitochondrial apoptotic pathway.