论文部分内容阅读
目的:探讨右美托咪定(dexmedetomidine, Dex)对CPB冠状动脉旁路移植术患者术后急性肾损伤(acute kidney injury, AKI)的影响及其相关机制。方法:择期行CPB冠状动脉旁路移植术的患者80例,年龄42~76岁,体重50~85 kg,性别不限,采用随机数字表法分为对照组(C组)和右美托咪定组(D组),每组40例。麻醉诱导前,D组给予静脉注射Dex负荷剂量0.6 μg/kg,15 min后以0.5 μg·kgn -1·hn -1的速度持续静脉泵注至术后24 h; C组以同样方法予以等容量生理盐水。分别于全身麻醉诱导前(Tn 0)、术毕(Tn 1)、术后24 h (Tn 2)、术后48 h (Tn 3)、术后72 h (Tn 4)时检测两组患者的心率、MAP、CVP、尿量,血清中Cr、BUN、IL-1β、TNF-α水平,外周血单个核细胞(peripheral blood mononuclear cell, PBMC)中NF-κB、caspase-3表达水平及Toll样受体(toll like receptor, TLR) 3细胞占比,记录两组患者术后48 h AKI发生率。n 结果:D组Tn 1~Tn 2时心率和MAP低于Tn 0(n P< 0.05),C组Tn 3~Tn 4时心率高于Tn 0(n P<0.05),Tn 1~Tn 3时D组心率和MAP低于C组(n P<0.05);两组Tn 2~Tn 4时血清Cr、BUN、IL-1β、TNF-α水平高于Tn 0(n P<0.05),Tn 3~Tn 4时D组血清Cr、BUN、IL-1β、TNF-α水平低于C组(n P<0.05);D组Tn 2~Tn 4时PBMC中TLR3细胞占比低于Tn 0 (n P<0.05),C组Tn 2~Tn 4时PBMC中TLR3细胞占比高于Tn 0(n P<0.05),Tn 2~Tn 4时D组PBMC中TLR3细胞占比低于C组(n P<0.05);两组患者Tn 2~Tn 4时PBMC中NF-κB表达水平高于Tn 0(n P<0.05),D组Tn 2~Tn 4时PBMC中NF-κB表达水平低于C组(n P<0.05);C组Tn 1~Tn 4时尿量较Tn 0减少(n P<0.05),D组Tn 2~Tn 3时尿量较Tn 0减少(n P<0.05),Tn 2~Tn 4时D组尿量多于C组(n P<0.05);C组AKI发生率高于D组(n P0.05)。n 结论:Dex预处理能显著降低CPB冠状动脉旁路移植术患者术后AKI的发生风险,其机制可能与抑制TLR3/NF-κB及其下游的炎症因子表达有关。“,”Objective:To investigate the effect of dexmedetomidine (Dex) on acute renal injury (AKI) in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (CPB) and potential mechanism.Methods:EEighty patients, aged 42 to 76 years old, weighing 50-85 kg and regardless of sex, who were scheduled for coronary artery bypass grafting with CPB were enrolled. According to the random number table method, they were divided into two groups (n n=40): a control group (group C) and a Dex group (group D). Before anesthesia induction, group D was intravenously injected with a loading dose of 0.6 μg/kg Dex, followed by after 15 min continuous intravenous pump infusion at a rate of 0.5 μg·kgn -1·hn -1 until 24 h after operation. Meanwhile, the same volume of normal saline was given to group C in the same way. Their heart rate, mean artery pressure (MAP), central venous pressure (CVP) and urine volume were detected before induction of general anesthesia (Tn 0), after surgery (Tn 1), and 24, 48 h and 72 h after operation (Tn 2, Tn 3, and Tn 4). The levels of serum creatinine (Cr), urea nitrogen (BUN), interleukin (IL)-1β, tumor necrosis factor (TNF)-α and the percentage of toll like receptor (TLR) 3 cells, nuclear factor-kappa B (NF-κB) and caspase-3 protein expression in peripheral blood mononuclear cells (PBMCs) were measured at Tn 0-Tn 4. The incidence of AKI 48 h after operation was recorded in both groups.n Results:The heart rate and MAP in group D at Tn 1-Tn 2 were lower than those at Tn 0 (n P<0.05), and the heart rate in group C at Tn 3-Tn 4 was higher than that at Tn 0 (n P<0.05). During Tn 1-Tn 3, the heart rate and MAP in group D were lower than those in group C (n P<0.05). For both groups, the levels of serum Cr, BUN, IL-1β and TNF-α at Tn 2-Tn 4 were higher than those at Tn 0, while the levels of serum Cr, BUN, IL-1β and TNF-α in group D at Tn 3-Tn 4 were lower than those in group C. The percentage of TLR3 cells in PBMCs at Tn 2-Tn 4 in group D at Tn 2-Tn 4 was lower than that at Tn 0 (n P<0.05), and the percentage of TLR3 cells in PBMCs in group C at Tn 2-Tn 4 was higher than that at Tn 0 (n P<0.05). The percentage of TLR3 cells in PBMCs in group D at Tn 2-Tn 4 was lower than that in group C (n P<0.05). For both groups, the expression of NF-κB in PBMCs at Tn 2-Tn 4 was higher than that at Tn 0, and the expression of NF-κB in PBMCs in group D at Tn 2-Tn 4 was lower than that in group C. The urine volumes at Tn 1-Tn 4 in group C were lower than that at Tn 0, and the urine volumes at Tn 2-Tn 3 in group D were lower than that in Tn 0. The incidence of AKI in group C was higher than that in group D (n P0.05).n Conclusions:Dex pretreatment can significantly reduce the risk of AKI after coronary artery bypass grafting with CPB, which may be related to the inhibition of TLR3/NF-κB and its downstream inflammatory mediators.