Neuroprotective effect of CTRP3 overexpression against sevoflurane anesthesia-induced cognitive dysfunction in aged rats through activating AMPK/SIRT1 and PI3K/AKT signaling pathways

Eur Rev Med Pharmacol Sci. 2020 May;24(9):5091-5100. doi: 10.26355/eurrev_202005_21202.


Objective: To investigate the effects of C1q/tumor necrosis factor-related protein-3 (CTRP3) on postoperative cognitive dysfunction (POCD) and elucidate the potential regulatory mechanism in sevoflurane anesthesia-induced aged rats.

Materials and methods: A sevoflurane anesthesia-induced POCD aged rat model was established and hematoxylin and eosin (H&E) staining was used to detect pathological changes of hippocampal neurons. Morris water maze task test was performed to determine the learning and memory ability of rats. Immunofluorescence, quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot were used to detect CTRP3 expression. Enzyme-linked immunosorbent assay (ELISA) or qRT-PCR assays were used to evaluate the changes of markers of brain damage and inflammatory cytokines. Terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assay was used to assess the apoptosis of nerve cells in hippocampus. Western blot assay were used to measure the expression levels of apoptosis-related protein, and AMP-activated protein kinase (AMPK)/SIRT1 and PI3K/AKT pathway.

Results: Sevoflurane exposure led to brain injury, cognitive dysfunction in aged rats and decreased the expression of CTRP3. Overexpression of CTRP3 could suppress nerve cell apoptosis, inhibit neuronal inflammation, reduce brain tissue damage and improve cognitive dysfunction of aged rats after sevoflurane anesthesia. Further studies showed that CTRP3 may play a role in POCD by regulating AMPK/SIRT1 and PI3K/AKT signaling pathways.

Conclusions: CTRP3 may effectively protect against sevoflurane-induced cognitive dysfunction and served as a potential predictive indicator and therapy target for POCD.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Adipokines / genetics
  • Adipokines / metabolism*
  • Aging / drug effects
  • Anesthetics, Inhalation
  • Animals
  • Apoptosis / drug effects
  • Cognitive Dysfunction / chemically induced
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / metabolism
  • Maze Learning / drug effects
  • Neuroprotective Agents / metabolism
  • Neuroprotective Agents / pharmacology*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Sevoflurane / antagonists & inhibitors
  • Signal Transduction* / drug effects
  • Sirtuin 1 / metabolism*


  • Adipokines
  • Anesthetics, Inhalation
  • C1q tumor necrosis factor-related protein 3, rat
  • Neuroprotective Agents
  • Sevoflurane
  • Proto-Oncogene Proteins c-akt
  • AMP-Activated Protein Kinases
  • Sirt1 protein, rat
  • Sirtuin 1