Esketamine alleviates hypoxia/reoxygenation injury of cardiomyocytes by regulating TRPV1 expression and inhibiting intracellular Ca ²⁺ concentration

Highlights

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  ESK treatment can increase H9c2 cell viability and reduce apoptosis and intracellular Ca ²⁺ concentration.

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  CAP treatment decreases H9c2 cell viability and increases apoptosis and intracellular Ca ²⁺ concentration.

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  TRPV1 upregulation decreases H9c2 cell viability and increases cell apoptosis and intracellular Ca ²⁺ concentration.

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  After overexpressing TRPV1, the protective effect of ESK on H/R injury of H9c2 cells is weakened.

Abstract

Objective

This study aimed to investigate the effect of Esketamine (ESK) on the Hypoxia/Reoxygenation (H/R) injury of cardiomyocytes by regulating TRPV1 and inhibiting the concentration of intracellular Ca ²⁺.

Methods

The H/R injury model of H9c2 cardiomyocytes was established after 4h hypoxia and 6h reoxygenation. H9c2 cells were treated with different concentrations of ESK or TRPV1 agonist capsaicin (10 μM) or TRPV1 inhibitor capsazepine (1 μM). Cell viability was detected by CCK-8 method, and apoptosis by flow cytometry. Intracellular Ca ²⁺ concentration was evaluated by Fluo-4 AM. LDH, MDA, SOD, and GSH-Px were detected with corresponding commercial kits. TRPV1 and p-TRPV1 proteins were detected by Western blot.

Results

After H/R, H9c2 cell viability decreased, apoptosis increased, intracellular Ca ²⁺ concentration increased, LDH and MDA levels increased, SOD and GSH-Px levels decreased, and p-TRPV1 expression increased. ESK treatment rescued these changes induced by H/R. After up-regulating TRPV1, the protective effect of ESK on H/R injury of H9c2 cells was weakened, while down-regulating TRPV1 could further protect against H/R injury.

Conclusion

ESK alleviates H/R injury of cardiomyocytes by regulating TRPV1 expression and inhibiting intracellular Ca ²⁺ concentration.