Effect of dexmedetomidine on TLR4/MyD88/NF-κB signaling pathway in peripheral blood mononuclear cells of elderly patients with diabetes mellitus undergoing lower extremity surgery

Abstract

Objective \nTo evaluate the effect of dexmedetomidine on Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor Kappa B (NF-κB) signaling pathway in the peripheral blood mononuclear cells of elderly patients with diabetes mellitus undergoing lower extremity surgery. \n \n \nMethods \nForty elderly patients of both sexes with type 2 diabetes mellitus, aged 65-80 yr, with body mass index of 18.5-27.9 kg/m2, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, with New York Heart Association Ⅰ or Ⅱ, undergoing lower extremity surgery with tourniquets under general anesthesia, were divided into 2 groups (n=20 each) by using a random number table method: control group (group C) and dexmedetomidine group (group D). Combined intravenous-inhalational anesthesia was applied.Dexmedetomidine was infused over 15 min in a dose of 1 μg/kg after induction of anesthesia, followed by a continuous infusion of 0.5 μg·kg-1·h-1 until the end of surgery in group D, while the equal volume of normal saline was given instead of dexmedetomidine in group C. Before using the the tourniquet and at 15 min, 1 h and 24 h after loosing the tourniquet, arterial blood samples were collected for determination of the expression of TLR4, NF-κB and MyD88 in peripheral blood mononuclear cells and concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) in plasma. \n \n \nResults \nCompared with group C, the expression of TLR4, NF-κB and MyD88 in peripheral blood mononuclear cells was significantly down-regulated, and the concentrations of TNF-α, IL-1β, cTnI and CK-MB in plasma were decreased at each time point after loosing the tourniquet in group D (P<0.05). \n \n \nConclusion \nThe mechanism by which dexmedetomidine reduces myocardial damage may be related to inhibiting TLR4/MyD88/NF-κB signaling pathway and reducing systemic inflammatory responses in elderly patients with diabetes mellitus undergoing lower extremity surgery. \n \n \nKey words: \nDexmedetomidine;\xa0Diabetes mellitus;\xa0Aged;\xa0Myocardial reperfusion injury;\xa0Toll-like receptor 4;\xa0Myeloid differentiation factor 88;\xa0NF-kappa B;\xa0Monocytes