甲基泼尼松龙对体外循环后细胞因子的影响及其肺保护作用的临床研究

目的:探讨甲基泼尼松龙(methylprednisolone,MPS)药物干预对体外循环后细胞因子TNF-α、IL-6、IL-8、IL-10的影响及其肺保护作用。方法:将30例心脏瓣膜置换术患者分为MPS组和对照组,两组麻醉、体外循环及心肌保护方法相同。MPS组术前静脉给予MPS 1g,术后分4次给予MPS 125mg/6h静脉注射,对照组给予相同剂量生理盐水。分别于T1=主动脉阻断前、T2=主动脉开放后5min、T3=主动脉开放后2h、T4=主动脉开放后6h、T5=主动脉开放后12h、T6=主动脉开放后24h、T7=主动脉开放后48h共7个时点抽取桡动脉血检测细胞因子TNF-α、IL-6、IL-8、IL-10血清水平变化;分别于以上前6个时点测动脉血氧分压(PaO2)、二氧化碳分压(PaCO2)、吸入氧浓度(FiO2)、算出肺泡动脉血氧分压差PA-aO2、呼吸指数RI和氧合指数OI=(PaO2/FiO2)。记录两组患者的ICU滞留时间以及气管插管拔除时间。结果:MPS组气管插管拔除时间10.24±2.12 h,对照组气管插管拔除时间14.31±1.32 h,MPS组少于对照组,差异有统计学意义(P<0.05);MPS组ICU滞留时间20.14±2.52 h,对照组ICU滞留时间20.32±2.82h,差异无统计学意义(P>0.05)。两组患者均治愈出院。MPS组及对照组分别进行PA-aO2、RI和PaO2/FiO2组内各时点比较差异有统计学意义(P<0.05)。两组间比较只有在T5和T6差异有统计学意义(P<0.05)。各时点对照组TNF-α、IL-6、IL-8水平明显高于MPS组,从T3到T5三个时点逐渐升高,到T6开始逐渐下降。MPS组IL-10水平从T2到T6明显高于对照组(P<0.001),在T3时点达到峰值。结论:MPS干预可抑制TNF-α、IL-6、IL-8等促炎细胞因子的释放,提高抗炎细胞因子IL-l0的水平,抑制了CPB后的炎症反应,减轻了肺损伤,对CPB术后有很好的肺保护作用。

Clinical study of methylprednisolone' influence on cytokines and its effect on lung protection after cardiopulmonary bypass

Objective: To evaluate the effect of corticosteroid treated drug of methylprednisolone(MPS) on the cytokines,such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-8(IL-8) and interleukin-10(IL-10) and its influence on lung injury protection after cardiopulmonary bypass(CPB).Methods: Thirty patients having undergone heart value replacement were divided randomly into two groups and received either preoperative MPS(n=15,protocol group) or no MPS(n=15,control group).The protocol group received 1g intravenous MPS preoperatively and 125mg doses were given every 6 hours after CPB in the intensive care unit(ICU),patients in the control group received similar volumes of isotonic sodium chloride solution.Blood samples were obtained from radial catheter at the following intervals:T1=before surgical operation,T2=5 minute after aortic cross-clamp release,T3=2 hours,T4=6 hours,T5=12 hours,T6=24 hours,T7= 48 hours after aortic cross-clamp release,and assayed for TNF-α,IL-6,IL-8,IL-10.Also,ventilatory measurements such as arterial oxygen pressure(PaO2),fraction of inspired oxygen(FiO2),alveolar-arterial oxygen gradient(PA-aO2),respiratory index(RI) and oxygenation index(OI= PaO2/ FiO2) were obtained at the same intervals.Extubation time and length of ICU stay were recorded in each group.Results: The extubation time in the MPS group was much shorter than in the control group(10.24±2.12vs 14.31±1.32h,P<0.05).The Lengths of ICU stay were similar in both groups(20.14±2.52 h vs 20.32±2.82h,P>0.05).Differences were significant within groups for PA-aO2,RI and PaO2/FiO2(P<0.05);nevertheless,differences were significant between groups only at T5 and T6 intervals.Serum cytokine levels were significantly different over times between groups: TNF-α,IL-6 and IL-8 were higher in the control group and peaked from T3 to T5 and got down from T6.The IL-10 level was high in the MPS group form T2 to T6(P<0.001),reaching a peak value at T3.Conclusions: Pharmacological interventions of MPS,by reducing proinflammatory cytokine such as TNF-α,IL-6,IL-8 release,increasing antiinflammatory cytokine IL-10 levels and inhibiting the systemic inflammatory response,may provide a better degree of lung protection in patients having undergone heart value replacement after CPB.