Dexmedetomidine Protects Cardiomyocytes against HypoxiaReoxygenation Injury by Suppressing TLR4-MyD88-NF-κB Signaling

Abstract EN

Objective.

We previously reported that dexmedetomidine (DEX) offers cardioprotection against ischemia/reperfusion injury in rats.

Here, we evaluated the role of toll-like receptors 4- (TLR4-) myeloid differentiation primary response 88- (MyD88-) nuclear factor-kappa B (NF-κB) signaling in DEX-mediated protection of cardiomyocytes using in vitro models of hypoxia/reoxygenation (H/R).

Methods.

The experiments were carried out in H9C2 cells and in primary neonatal rat cardiomyocytes.

Cells pretreated with vehicle or DEX were exposed to hypoxia for 1 h followed by reoxygenation for 12 h.

We analyzed cell viability and lactate dehydrogenase (LDH) activity and measured tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β mRNA levels, TLR4, MyD88, and nuclear NF-κB p65 protein expression and NF-κB p65 nuclear localization.

TLR4 knock-down by TLR4 siRNA transfection and overexpression by TLR4 DNA transfection were used to further confirm our findings.

Results.

DEX protected against H/R-induced cell damage and inflammation, as evidenced by increased cell survival rates, decreased LDH activity, and decreased TNF-α, IL-6, and IL-1β mRNA levels, as well as TLR4 and NF-κB protein expression.

TLR4 knock-down partially prevented cell damage following H/R injury, while overexpression of TLR4 abolished the DEX-mediated protective effects.

Conclusions.

DEX pretreatment protects rat cardiomyocytes against H/R injury.

This effect is partly mediated by TLR4 suppression via TLR4-MyD88-NF-κB signaling.