心脏直视手术过程中循环细胞因子的变化及其与术后肾、肺功能改变的关系

张国华; 侯凡凡; 王武军; 张训; 吴华; 刘志强; 陶惠琴

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中国血液净化 ›› 2005, Vol. 4 ›› Issue (9) : 500-503.

论著

心脏直视手术过程中循环细胞因子的变化及其与术后肾、肺功能改变的关系

张国华1 侯凡凡1 王武军2 张训1 吴华2 刘志强1 陶惠琴1

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摘要

目的观察心脏手术患者体外循环（CPB）过程中循环促炎症细胞因子和抗炎症细胞因子的动态变化及其与术后肺、肾功能变化的关系。方法南方医科大学南方医院选择2002年10月～2003年12月15例风湿性心脏病(RHD)患者，在换瓣术前、手术过程中及术后不同时间点测定血浆肿瘤坏死因子(TNF- α)、白细胞介素－6(IL－6)、白细胞介素-8(IL－8)、白细胞介素-10(IL-10)、白细胞介素－1受体拮抗剂（IL-1ra）、C-反应蛋白（CRP）水平，并观察循环细胞因子水平与肾、肺功能变化的关系。结果 ①CPB开始后TNF－α、IL－6、IL－8、CRP、IL－10、IL-1ra水平均较术前明显升高 (P均＜0.05)，促炎症因子TNF－α、IL－6水平在CPB结束时达峰值。而IL－8水平在CPB结束后2h达峰值；抗炎症因子IL－10在CPB结束时均达峰值，IL-lra在CPB结束后2h达峰值。CRP水平于CPB结束后第二天达峰值，为(141.14±27.81) mg/L。CPB结束时，IL－8和IL－6均与IL－10呈正相关(r= 0.509, P＜0.01；r=0.418, P＜0.01), IL－6还与CRP呈正相关(r=0.452, P＜0.01); ②CPB结束后第一天，2/15例发生急性肾衰竭，9/15例尿蛋白超过正常上限，所有患者N-乙酰-β-D-葡萄糖酐酶(NAG水平均升高。尿NAG酶水平与CPB结束后的TNF-α水平存在正相关(r=0.501, P＜0.01)。Ccr与术后CRP呈负相关(r=－0.404, P＜0.05) ③CPB结束时气道平台压（PPlateau）已明显升高，CPB结束后1h达峰值，明显高于术前水平, P＜0.01。气道峰压（PPeak）在CPB结束后1h亦明显高于术前, P＜0.01。CPB结束后1h的TNF-α水平与PPeak 呈正相关(r=0.472, P<0.01)。结论心脏换瓣术过程中循环促炎症细胞因子、抗炎症细胞因子均明显升高,细胞因子IL－6水平与全身炎症反应标志物CRP呈正相关。促炎症因子水平与术后肾、肺功能损害密切相关,提示清除循环炎症因子可能是防治心脏手术后肾、肺损害的干预方法。

Abstract

Objective To observe the dynamic changes of plasma pro-inflammatory and anti-inflammatory cytokines during open-heart surgery with cardiopulmonary by pass(CPB) and their relationships with postoperative renal and respira-tory dysfunction. Methods Blood samples from 15 patients undergoing valve replacement with CPB were analysed for tumor necrosis factor α (TNF-α, interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), interleukin 1 receptor antagonist (IL-1ra) and C- reactive protein (CRP). Results ①The plasma levels of TNF－α、IL－6、IL－8、CRP、IL－10 and IL-1ra were significantly elevated after CPB started (P<0.05 all). Peak values of TNF－αand IL－6 were (12.67±2.78) pg/ml and (133.71±29.13) pg/ml respectively at the end of CPB. Peak values of IL－8 was (101.31±31.82) pg/ml at two hours after the end of CPB. Plasma CRP was significantly increased and reached peakvalue of (141.14±27.81) mg/L at two days after the operation. There was a close correlation between the level of IL－10 and CRP (r=0.452, P<0.01). ② Acute renal failure occurred in 2/15 patients one day after the operation, the urinary protein excretion increased in 9/15 patients and all patients showed increased urinary N-acetyl-β D-glycosaminidase (NAG). The levels of urinary NAG was correlated with plasma level of TNF－α (r=0.501, P <0.01), and a negative correlation could be seen between creatinine clearance (Ccr) and CRP levels (r=-0.404, P <0.05). ③Plateau airway pressure(PPlateau) and Peak airway pressure (PPeak) increased to peak value at 60 min after the end of CPB. The PPeak was correlated with plasma TNF－α(r=0.472, P<0.01). Conclusions Plasma pro-inflammatory and anti-inflammatory cytokines were significantly elevated during CPB. The levels of pro-inflammatory cytokines levels were closely associated with lung and kidney dysfunction after CPB. Decreasing the levels of pro-inflammatory cytokines might be a potential intervention for CPB-induced lung and kidney injury.