Dexmedetomidine Preconditioning For Myocardial Protection In Ischemia–reperfusion Injury In Rats By Downregulation Of The HMGB1-TLR4-NF-κB Signaling Pathway

Objective To observe whether dexmedetomidine preconditioning could induce a myocardio-protective effect against ischemia–reperfusion(I–R)injury by inhibiting associated inflammatory processes through downregulation of the high mobility group box1(HMGB1)–toll-like receptor 4(TLR4)–nuclear factor κB(NF-κB)signaling pathway.Methods Seventy rats were randomly assigned to 7 groups: a control and 6 test groups,involving ischemia–reperfusion for 30 and 120 minutes,respectively,in isolated rat hearts and different pretreatment protocols with dexmedetomidine(10 n M)as well as yohimbine(1 μM)and recombinant HMGB1 peptide(r HMGB1;20 μg/L),alone or in combination with dexmedetomidine.Cardiac function was recorded;myocardial HMGB1,TLR4,and NF-κB activities and levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were measured as were lactate dehydrogenase(LDH)and creatine kinase(CK)in coronary outflow.Results Dexmedetomidine preconditioning significantly improved cardiac function(P<0.05),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<0.05).All of these effects were partially reversed by yohimbine(P<0.05)or r HMGB1(P<0.05).Conclusion Dexmedetomidine preconditioning alleviated myocardial I–R injury in rats through inhibition of inflammatory processes associated with downregulation of the HMGB1–TLR4–NF-κB signaling pathway via activation at α2-adrenergic receptors.