环孢素A对体外循环心脏手术患者炎症介质的影响

Effects of cyclosporin A on inflammatory mediators in patients undergoing cardiac surgery with cardiopulmonary bypass

目的:探讨环孢素A(CsA)对体外循环(CPB)心脏手术患者炎症介质的影响及其减轻CPB术后全身炎症反应的机制.方法:将50例CPB下心脏手术患者随机分为对照组(n=25)和实验组(n=25).实验组患者术前预充液中加入CsA,2mg/kg,其他药物与对照组相同.分别于手术麻醉前、CPB开始后及CPB结束0,12,24,48h测定两组患者的IL-1β,IL-6和肿瘤坏死因子α(TNF-α)水平.建立CPB前和CPB结束时在右心耳切口缘取心肌,Westernblot测定心肌pAkt、核转录因子κB(NF-κBp65)表达.结果:两组TNF-α,IL-1β,IL-6水平在CPB开始后上升,CPB后12h达高峰;CsA治疗组TNF-α,IL-1β,IL-6水平从CPB后12h显著低于对照组(P<0.05).CPB后两组pAkt表达与CPB前相比均显著增加(P<0.05),CsA治疗CPB后pAkt表达较常规治疗组显著降低(P<0.05).两组CPB后NF-κBp65表达与未干预组相比均显著增加(P<0.05);CsA治疗CPB后NF-κBp65表达较常规治疗组显著降低(P<0.05).结论:CsA可减轻CPB心脏手术患者术后全身炎症反应,可能是通过抑制Akt活化、减弱NF-κB的活化实现的.

AIM：To investigate the effects of cyclosporin A on inflammatory mediators in patients undergoing cardiac surgery with cardiopulmonary bypass and the mechanisms. METHODS： A total of 50 patients were randomly assigned to control group and CsA group, with 25 patients in each group. Levels of IL-1β, IL-6 and TNF-α in both groups were respectively measured before surgical anesthesia, 0 h after the initiation of cardiopulmonary bypass （ CPB）, and 0, 12,24 and 48 h after the termination of CPB. Western blot analysis was used to examine pAkt and NF-KBp65 expressions in cardiomyocytes pre- and post-CPB. RESULTS：In both groups, TNF-α, IL-1β and IL-6 levels were increased since the initiation of CPB, and reached the peak at 12 h after the termination of CPB , then it began to decrease. Compared with control group , the levels since 12 h after the termination of CPB were lower in CsA group （ P 〈 0. 05 ）. Compared with pre-CPB, pAkt expression in cardiomyocytes in both groups was increased post- CPB（P 〈0.05）, and after CsA therapy, it was significantly decreased （ P 〈 0.05 ）. Compared with pre-CPB, NF-KBp65 expression in cardiomyocytes was increased in both groups （P 〈 0.05）, and after CsA therapy, it was significantly decreased （P 〈 0.05）. CONCLUSION ： Cyclosporin A decreases systemic inflammatory reaction in patients undergoing cardiovascular surgery with CPB through inhibiting Akt activation and decreasing NF-κB activation in cardiomyocytes.