七氟醚预处理对体外循环下心脏瓣膜置换术患者外周血白细胞核因子-κB活性的影响

Effects of sevoflurane pretreatment on the nuclear factor kappa B-DNA binding activity of leukocyte in peripheral blood of the patients undergoing cardiac valve replacement with cardiopulmonary bypass

目的探讨七氟醚预处理对体外循环下心脏瓣膜置换术患者外周血白细胞核因子-κB(NF-κB)活性的影响及其与心肌缺血/再灌注损伤的关系。方法20例拟在体外循环下行二尖瓣和(或)主动脉瓣置换术患者随机分成两组:对照组(C组)和七氟醚预处理组(S组),每组各10例。两组均采用静脉注射咪唑安定0.08～0.12mg·kg-1、芬太尼5～10μg·kg-1、维库溴铵0.1mg·kg-1施行麻醉诱导;气管插管后,吸纯氧机械控制通气。麻醉维持C组采用间断静脉注射芬太尼和咪唑安定,S组采用七氟醚2MAC持续吸入,并间断静脉注射芬太尼和咪唑安定;两组均按需追加维库溴胺维持肌肉松弛。CPB前两组患者收缩压均维持在90～120mmHg。CPB开始时停用七氟醚吸入,之后两组均采用同样方法维持麻醉。芬太尼总量C组为40～60μg·kg-1,S组为20～30μg·kg-1。于麻醉诱导插管后即刻(T0)和主动脉开放后30min(T1)、1h(T2)、2h(T3)、6h(T4),分别采桡动脉血3ml,共15ml,并分离提取白细胞,用凝胶电泳迁移率改变分析法(electrophoretic mobility shift assay,EM-SA)测定白细胞NF-κB活性,并记录两组患者心脏复跳情况、多巴胺以及硝普纳用量。结果与S组各观测点相比较,除T0外,C组各点白细胞NF-κB活性均增加(P<0.05或0.01),且开放主动脉30min时达到高峰;而S组各点NF-κB活性无明显变化。自动复跳/电击复跳比例C组为4/6,S组为8/2,S组明显高于C组(P<0.01);硝普纳用量两组比较差异无统计学意义(P>0.05);多巴胺用量C组明显多于S组(P<0.01),且两组患者多巴胺用量与各自EMSA结果的最高值呈正相关,相关系数r=0.994(P<0.01)。结论七氟醚预处理可抑制体外循环下瓣膜置换术患者外周血白细胞NF-κB的活性。

Aim To investigate the effect of sevoflurane pretreatment on the nuclear factor kappa B （NF-kB）- DNA binding activity of leukocyte in peripheral blood of the patients undergoing cardiac valve replacement under cardiopulmonary bypass （ CPB ）. Methods Twenty patients undergoing cardiac valve replacement under CPB were divided randomly into two groups： control group （group C ） and sevoflurane pretreatment group （group S）. All patients were induced with midazolam 0. 08 -0, 12 mg·kg^-1 , fentanyl 5 - 10 ug·kg^-1 and vecuronium 0. 1 mg ·kg^-1. After endotracheal intubation, mechanical ventilation was conducted with 100% oxygen. Anesthesia in group C was maintained with intermittent intravenous fentanyl and midazolam, while in group S maintained with 2MAC sevoflurane besides fentanyl and midazolam intermittently before CPB. The anesthesia depth was kept to maintain the systolic pressure within 90 - 120 mmHg in both groups. Sevoflurane was discontinued at the initiation of CPB, and the following anesthetic regimen was the same as that in group C. To examine the NF-kB- DNA binding activity, the arterial blood samples were withdrawn at the following time point： after endotracheal intubation and before inhaling sevoflurane （TO ） , 30 min （T1）, 1 h （T2）,2h （T3）,6h （T4） after aortic de-clamping. Electrophoretic mobility shift assay （EMSA） was used to measure the NF-kB-DNA binding activity of leukocyte. The dosage of fentanyl, midazolam, dopamine, sodium nitroprusside and the rate of spontaneous heart resuscitation in both groups were recorded. Results The NF-kB-DNA binding activity in group C was increased significantly after aortic de-clamping, and it reached to maximum at T1, but it was not changed significantly in group S from TO to T4. The value of EMSA at all time points was lower in group S except TO than that in group C （P 〈0. 01 ）. The rate of spontaneous heart resuscitation was significantly higher in group S than that in group C （P 〈0.01 ） ; the total amount of fentanyl was 40 - 60 ug·kg^-1 in group C, and 20 -30ug·kg^-1 in group S and less dopamine was used in group S （ P 〈 0. 01 ） , while sodium nitroprusside used did not show significant difference in both groups, and the total amount of dopamine used of each patient in both groups was positively correlated with the maximum value of EMSA （ r = 0. 994, P 〈 0. 01 ）. Conclusion Sevoflurane pretreatment can attenuate the NF-kB-DNA binding activity of leukocyte in peripheral blood of the patients undergoing cardiac valve replacement under cardiopulmonary bypass.