Research Paper Volume 16, Issue 4 pp 3763—3772
Liraglutide improves sevoflurane-induced postoperative cognitive dysfunction via activating autophagy and inhibiting apoptosis
- 1 Department of Endocrinology and Metabolism, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China
- 2 Jiangxi Clinical Research Center for Endocrine and Metabolic Disease, Nanchang 330006, Jiangxi, China
- 3 Jiangxi Branch of National Clinical Research Center for Metabolic Disease, Nanchang 330006, Jiangxi, China
- 4 Department of Anesthesiology and Operative medicine, Medical Center of Anesthesiology and Pain, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China
- 5 Department of Anesthesiology, Medical Center of Anesthesiology and Pain, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China
Received: October 18, 2023 Accepted: January 11, 2024 Published: February 15, 2024
https://doi.org/10.18632/aging.205558How to Cite
Copyright: © 2024 Hu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Postoperative cognitive dysfunction (POCD) is a common postoperative complication in elderly patients. Liraglutide (LRG) has high homology (97%) with natural glucagon like peptide-1, and it has been proved to be effective in some nervous system diseases. Whether LRG could regulate POCD has not been reported.
Methods: Sevoflurane (Sev) was used to simulate postoperative cognitive dysfunction (POCD) model. Morris water maze test was performed to evaluate the memory ability and neurological function of rats. Escape latency, swim distance, crossing platform times, average velocity, and targeting quadrant time were analyzed. The cell apoptosis, mRNA and protein expression were measured through flow cytometry, PCR, and western blotting, respectively.
Results: LRG significantly improved the memory ability and neurological function of Sev-treated rats, but 3-MA reversed the effects of LRG. LRG remarkably inhibited apoptosis but up-regulated autophagy related proteins both in vivo and in vitro levels. However, knocking down AMPK could markedly reverse the influence of LRG on apoptosis, autophagy, and cell apoptosis.
Conclusions: LRG induced autophagy activation can maintain cell homeostasis and promote cell survival by blocking the apoptotic pathway. LRG could improve Sev-induced POCD via activating autophagy, inhibiting apoptosis, and regulating AMPK/mTOR signaling pathway. This study provides a novel therapeutic strategy for the prevention and treatment of POCD.
Abbreviations
POCD: Postoperative cognitive dysfunction; Sev: Sevoflurane; LRG: Liraglutide; mTOR: Mammalian target of rapamycin; AMPK: AMP activated protein kinase.