Abstract:Objective: To investigate the effect of oleuropein on cochlear tissue damage in noise-induced hearing loss (NIHL) rats by regulating the proline-rich Akt substrate of 40 kDa (PRAS40)/mammalian rapamycin target protein complex 1 (mTORC1) signaling pathway. Methods: A total of 48 rats were selected, and 12 rats were randomly regarded as the NC group. The remaining rats were used to construct a NIHL rat model using white noise. Subsequently, NIHL model rats were randomly grouped into a Model group, an oleuropein group (50 mg/kg), and an oleuropein+NV-5138 group (50 mg/kg+160 mg/kg mTORC1 activator). The condition of rats in each group was observed, and the auditory brainstem response (ABR) threshold of rats in each group was evaluated; hematoxylin-eosin (HE) staining was applied to detect pathological damage in cochlear tissue; TUNEL was applied to observe the apoptosis of cochlear tissue; Confocal microscopy (DAPI staining) was applied to observe changes in the sequence of hair cells in the cochlear basement membrane; Western blot was applied to detect the expression of PRAS40, phosphorylated PRAS40 (p-PRAS40), phosphorylated mTORC1 (p-mTORC1), mTORC1, and Bax proteins in rat cochlear tissue. Results: Compared with the NC group, the ABR threshold and apoptosis number of rats in the Model group increased, the pathological damage to cochlear tissue increased, the expression of p-mTORC1/mTORC1 and Bax proteins increased, basal membrane hair cell sequence was damaged, the expression of p-RAS40/PRAS40 protein decreased (P<0.05); compared with the Model group, the ABR threshold and apoptosis number of rats in the oleuropein group decreased, the pathological damage of cochlear tissue alleviated, the expression of p-mTORC1/mTORC1 and Bax proteins decreased, basal membrane hair cell sequence was neat, the expression of p-PRAS40/PRAS40 protein increased (P<0.05); the corresponding experimental detection results in the oleuropein+NV-5138 group were opposite to those in the oleuropein group, and the damage in the rats worsened. The intervention of NV-5138 weakened the improvement effect of oleuropein on cochlear tissue damage in NIHL rats (P<0.05). Conclusion: Oleuropein may alleviate cochlear tissue damage in noise-induced hearing loss rats by promoting the PRAS40/mTORC1 signaling pathway.