Dexmedetomidine preconditioning for myocardial protection in ischaemia-reperfusion injury in rats by downregulation of the high mobility group box 1-toll-like receptor 4-nuclear factor κB signalling pathway

Yu Fan Yang, Ke Peng, Hong Liu, Xiao Wen Meng, Jing Jing Zhang, Fu Hai Ji

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Pharmacological preconditioning reduces myocardial infarct size in ischaemia-reperfusion (I-R) injury. Dexmedetomidine, a selective α2-adrenoceptor agonist, has a proven cardioprotective effect when administered prior to I-R, although the underlying mechanisms for this effect are not fully understood. We evaluated whether dexmedetomidine preconditioning could induce a myocardio-protective effect against I-R injury by inhibiting associated inflammatory processes through downregulation of the high mobility group box 1 (HMGB1)-toll-like receptor 4 (TLR4)-nuclear factor κB (NF-κB) signalling pathway. Seventy rats were randomly assigned to seven groups: a control and six test groups, involving I-R for 30 and 120 minutes, respectively, in isolated rat hearts and different pretreatment protocols with dexmedetomidine (10 nmol/L) as well as yohimbine (1 μmol/L) and recombinant HMGB1 peptide (rHMGB1; 20 μg/L), alone or in combination with dexmedetomidine. Cardiac function was recorded; myocardial HMGB1, TLR4, and NF-κB activities and levels of tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured as were lactate dehydrogenase (LDH) and creatine kinase (CK) in coronary outflow. Dexmedetomidine preconditioning significantly improved cardiac function (P<.05), downregulated the expression of HMGB1-TLR4-NF-κB, reduced levels of TNF-α and IL-6 in isolated ventricles during I-R injury, and significantly reduced CK and LDH levels in coronary outflow (P<.05). All of these effects were partially reversed by yohimbine (P<.05) or rHMGB1 (P<.05). Dexmedetomidine preconditioning alleviated myocardial I-R injury in rats through inhibition of inflammatory processes associated with downregulation of the HMGB1-TLR4-NF-κB signalling pathway via activation at α2-adrenergic receptors.

Original languageEnglish (US)
Pages (from-to)353-361
Number of pages9
JournalClinical and Experimental Pharmacology and Physiology
Volume44
Issue number3
DOIs
StatePublished - Mar 1 2017

Keywords

  • dexmedetomidine
  • high mobility group box 1-toll-like receptor 4-nuclear factor κB
  • myocardial protection
  • preconditioning

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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