Rapamycin improves sevoflurane‑induced cognitive dysfunction in aged rats by mediating autophagy through the TLR4/MyD88/NF‑κB signaling pathway.

Abstract

The present study was aimed to observe the protective effect of rapamycin on cognitive dysfunction induced by sevoflurane in aged rats and its effect on autophagy-related proteins, and to investigate the regulatory mechanism of the Toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor-κB (TLR4/MyD88/NF-κB) signaling pathway. Fifty Sprague-Dawley rats were randomly assigned to a control group, a sevoflurane group, a rapamycin pretreatment group, a TLR4 inhibitor group and a 3MA autophagy inhibitor group. A water maze test was used to evaluate the cognition and memory of rats. Hematoxylin and eosin (H&E) staining was performed to observe pathological changes of brain tissue. A TUNEL assay was used to detect the apoptosis of brain tissue. ELISA was used to assess changes in brain injury markers and inflammatory factors. A western blot assay or quantitative reverse transcription PCR (RT-qPCR) were performed to determine the expression of autophagy-related proteins and the TLR4/MyD88/NF-κB signaling pathway in brain tissue. The results revealed that rapamycin could improve cognitive dysfunction of aged rats induced by sevoflurane. Rapamycin was identified to play a therapeutic role, including mitigating brain tissue damage, inhibiting apoptosis, and activating autophagy in a sevoflurane-treated aged rat model. This function of rapamycin was demonstrated to depend on the TLR4/MyD88/NF-κB signaling pathway.