Esketamine improves hypoxic-ischemic myocardial injury in neonatal rats by glycogen synthase kinase-3β/NOD-like receptor thermal protein domain-containing protein 3 pathway

LIU Xinyan; DONG Liyun; ZHOU Peipei; CHEN Yongxue; WANG Xinbo; SUN Yan

doi:10.7619/jcmp.20240407

Journal of Clinical Medicine in Practice > 2024 > 28(15): 19-25. > DOI: 10.7619/jcmp.20240407

LIU Xinyan, DONG Liyun, ZHOU Peipei, CHEN Yongxue, WANG Xinbo, SUN Yan. Esketamine improves hypoxic-ischemic myocardial injury in neonatal rats by glycogen synthase kinase-3β/NOD-like receptor thermal protein domain-containing protein 3 pathway[J]. Journal of Clinical Medicine in Practice, 2024, 28(15): 19-25. DOI: 10.7619/jcmp.20240407

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Esketamine improves hypoxic-ischemic myocardial injury in neonatal rats by glycogen synthase kinase-3β/NOD-like receptor thermal protein domain-containing protein 3 pathway

1.
Department of Anesthesiology, Handan Central Hospital of Hebei Province, Handan, Hebei, 056001
2.
Department of Anesthesiology, the Affiliated Hospital of Hebei University of Engineering, Handan, Hebei, 056038

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Received Date: January 22, 2024
Revised Date: April 16, 2024

Graphical Abstract

Abstract

Abstract

Objective
To investigate the effects of esketamine on hypoxic-ischemic myocardial injury in neonatal rats based on glycogen synthase kinase-3β/NOD-like receptor thermal protein domain-containing protein 3 (GSK-3β/NLRP3) pathway.
Methods
Thirty neonatal rats were randomly divided into sham operation group, model group and esketamine group, with 10 rats in each group. The rats in the sham operation group underwent a median incision in the neck to expose the bilateral common carotid arteries; the rats in the model group and the esketamine group underwent ligation of the common carotid arteries combined with a hypoxic environment to establish a model ofischemia and hypoxia; the rats in the esketamine group were given esketamine intervention (50 mg/kg). Left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), serum creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI), lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1β levels, myocardial injury, myocardial cell apoptosis and apoptosis protein caspase 1/3/9 levels, neutrophil infiltration in myocardial tissue, and changes in GSK-3β and NLRP3 protein levels in myocardial tissue were detected in each group.
Results
Compared with the sham operation group, the LVEF and LVFS were significantly decreased and the LVEDD and LVESD were significantly increased in the model group, while the LVEF and LVFS were significantly higher and the LVEDD and LVESD were significantly lower in the esketamine group than in the model group (P < 0.05). The serum levels of CK-MB, cTnI, LDH, TNF-α, IL-6, IL-1β, myocardial injury and apoptosis, caspase 1/3/9 protein levels in myocardial tissue sections, neutrophil counts, and GSK-3β and NLRP3 protein levels were significantly increased in the model group, and these indicators were significantly lower in the esketamine group than in the model group (P < 0.05).
Conclusion
Esketamine improves hypoxic-ischemic myocardial injury in neonatal rats by inhibiting inflammation, and its mechanism of action is related to the GSK-3β/NLRP3 pathway.

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References (20)

References

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Esketamine improves hypoxic-ischemic myocardial injury in neonatal rats by glycogen synthase kinase-3β/NOD-like receptor thermal protein domain-containing protein 3 pathway