右美托咪定对体外循环下心内直视手术患者外周血单核细胞信号通路的影响

Effect of dexmedetomidine on TLRs/My D88/NF-κB signal pathway in patients undergoing cardiac surgery under cardiopulmonary bypass

目的评价右美托咪定对体外循环(CPB)下心内直视手术患者外周血单核细胞Toll样受体(TLRs)/髓样分化因子(My D)88/核转录因子(NF)-κB信号通路的影响。方法择期在CPB下行心脏瓣膜置换术患者90例,年龄30~64岁,体重45~68 kg,ASA分级Ⅱ或Ⅲ级,NYHA心功能分级Ⅱ或Ⅲ级,左室射血分数>50%,采用随机数字表法分为3组(n=30):右美托咪定组1(D1组)、右美托咪定组2(D2组)和对照组(C组)。D1组和D2组分别在麻醉诱导前静脉泵注右美托咪定0.5μg/kg和1.0μg/kg负荷量,随后分别以0.2μg/(kg·h)和0.4μg/(kg·h)速率输注至术毕,C组则以等容量生理盐水代替。分别在麻醉诱导前(T0)、CPB后1 h(T1)、3 h(T2)、5 h(T3)、12 h(T4)和24 h(T5)这6个时间点采集血标本,采用流式细胞仪检测外周血CD14+单核细胞TLR2、TLR4和NF-κB的表达量及My D88的平均荧光强度;采用ELISA法检测血浆中肿瘤坏死因子-α(TNF-α)浓度。结果与T0比较,三组患者在T1~T5时外周血CD14+单核细胞TLR2、TLR4和NF-κB阳性表达率及My D88荧光强度,血浆中TNF-α浓度均增高(P<0.05);与C组比较,D1和D2组在T1~T5时外周血CD14+单核细胞TLR2、TLR4和NF-κB阳性表达率及My D88荧光强度,血浆中TNF-α浓度均降低(P<0.05);与D1组比较,D2组在T1~T5时外周血CD14+单核细胞TLR2、TLR4和NF-κB阳性表达率和My D88荧光强度,血浆中TNF-α浓度均降低(P<0.05)。结论右美托咪定减轻CPB下心内直视手术患者全身炎症反应且呈剂量依赖,其机制与抑制TLRs/My D88/NK-κB信号通路的激活有关。

Objective To evaluate the effect of dexmedetomidine on TLRs/My D88/NF-κB signaling pathway in patients undergoing cardiac surgery under cardiopulmonary bypass（ CPB）. Methods Ninety patients aged 30-64 years,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ（ New York Heart Association classification Ⅱor Ⅲ）,with the left ventricular ejection fraction50%,scheduled for elective cardiac valve replacement surgery with CPB,were divided into three groups（ n = 30 each） using a random number table： dexmedetomidine group one（ group D1）,dexmedetomidine group two（ group D2） and control group（ group C）. In group D1 and D2,a 0.5 μg/kg（ group D1） and 1.0 μg/kg（ group D2） bolus dose of dexmedetomidine were administered before the induction of anesthesia,followed by a 0.2 μg/（ kg·h）（ group D1） and 0.4 μg/（ kg·h）（ group D2） infusion until the end of operation,while in group C equal volume of normal saline was infused instead of dexmedetomidine. Before anesthesia induction（ T0）,at 1 h,3 h,5 h,12 h,and 24 h（ T1-T5） after termination of CPB,blood samples were collected to detect the expression levels of toll-like receptor 2 and 4（ TLR2,4）,myeloid differentiation factor 88（ My D88） and nuclear factor Kappa B（ NF-κB） in peripheral blood CD14＋mononuclear cells using flow cytometry and to measure the concentrations of tumor necrosis factor-alpha（ TNF-α） in plasma by enzyme-linked immunosorbent assay. Results Compared with group C,the expression levels of TLR2,4,My D88 and NF-κB in peripheral blood and CD14＋mononuclear cells were significantly decreased,the concentrations of TNF-α were significantly decreased at1 h,3 h,5 h,12 h,and 24 h（ T1-T5） after termination of CPB in group D1 and group D2（ P 0.05）. Compared with group D1,the expression levels of TLR2,4,My D88 and NF-κB in peripheral blood and CD14＋mononuclear cells were significantly decreased,the concentrations of TNF-α were significantly decreased at 1 h,3 h,5 h,12 h,and 24 h（ T1-T5） after termination of CPB in group D2（ P 0.05）. Conclusions The mechanism by which dexmedetomidine reduces inflammatory responses is related to inhibition of the activation of TLRs/My D88/NF-κB signaling pathway in a dose-dependent manner in patients undergoing cardiac surgery under CPB.