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

Li,Yan; Liu,Lidan; Tian,Yue; Zhang,Jin

doi:10.3892/mmr.2019.10541

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

Authors:
- Yan Li
- Lidan Liu
- Yue Tian
- Jin Zhang
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Affiliations: Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
Published online on: July 31, 2019 https://doi.org/10.3892/mmr.2019.10541
Pages: 3085-3094
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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