右美托咪定对下肢手术糖尿病老年患者外周血单核细胞TLR4/MyD88/NF-κB信号通路的影响

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

目的评价右美托咪定对下肢手术糖尿病老年患者外周血单核细胞Toll样受体(TLRs)/髓样分化因子(MyD)88/NF-κB信号通路的影响.方法择期全麻下行骨科下肢手术需用止血带2型糖尿病老年患者40例,年龄65~80岁,性别不限,体重指数18.5~27.9 kg/m^2,ASA分级Ⅱ或Ⅲ级,NYHA功能分级Ⅰ或Ⅱ级,采用随机数字表法分为2组(n=20):对照组(C组)和右美托咪定组(D组).采用静吸复合麻醉.麻醉诱导后D组经15 min静脉输注右美托咪定1μg/kg,继之以0.5μg·kg^-1·h^-1的速率维持至术毕,C组给予等容量生理盐水.分别于上止血带前、松开止血带后15min、1和24 h时,采集动脉血标本,检测外周血单核细胞TLR4、NF-κB和MyD88的表达水平,检测血浆TNF-α、IL-1β、cTnI和CK-MB浓度.结果与C组比较,D组松开止血带后各时点外周血单核细胞TLR4、NF-κB和MyD88表达下调,血浆TNF-α、IL-1β、cTnI和CK-MB的浓度降低(P<0.05).结论右美托咪定减轻下肢手术糖尿病老年患者心肌损伤的机制可能与抑制TLR4/MyD88/NF-κB信号通路,减轻全身炎症反应有关.

Objective To 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 pe-ripheral blood mononuclear cells of elderly patients with diabetes mellitus undergoing lower extremity surger-y. Methods Forty elderly patients of both sexes with type 2 diabetes mellitus, aged 65-80 yr, with body mass index of 18. 5-27. 9 kg/m^2 , 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 1μg/kg after induction of anesthesia, fol-lowed 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 determi-nation of the expression of TLR4, NF-κB and MyD88 in peripheral blood mononuclear cells and concentra-tions of tumor necrosis factor-alpha ( TNF-α), interleukin-1β( IL-1β), cardiac troponin I ( cTnI ) and creatine kinase-MB ( CK-MB) in plasma. Results Compared with group C, the expression of TLR4, NF-κB and MyD88 in peripheral blood mononuclear cells was significantly down-regulated, and the concentra-tions 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). Conclusion The mechanism by which dexmedetomidine reduces myo-cardial 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.