Objective To evaluate the effect of dexmedetomidine on TLRs/MyD88/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 Ⅱ or Ⅲ), with the left ventricular ejection fraction ＞50％, 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 (TO), atlh, 3h, 5h, 12h, 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 (MyD88) and nuclear factor KappaB(NF-κB) in peripheral blood CD 14+ 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, MyD8B 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 D1 and group D2 (P ＜0.05). Compared with group D1, the expression levels of TLR2, 4, MyD88 and NF-κB in peripheral blood and CD14+ mononuclear cells were significantly decreased, the concentrations of TNF-α were significantly decreased at 1h, 3h, 5h, 12h, 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/MyD88/NF-κB signaling pathway in a dose-dependent manner in patients undergoing cardiac surgery under CPB.%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(MyD)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1.0 μg/kg负荷量,随后分别以0.2 μg/(kg · h)和0.4 μg/(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MyD88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MyD88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MyD88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MyD88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/MyD88/NK-κB信号通路的激活有关.
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