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心脏手术后外周血单个核细胞中肿瘤坏死因子-α和白细胞介素-10基因的表达

Tumor necrosis factor-alpha and interleukin-10 gene expression in peripheral blood mononuclear cells after cardiac surgery.

作者信息

Duggan Edel, Caraher Emma, Gately Kathy, O'Dwyer Michael, McGovern Eilis, Kelleher Dermot, McManus Ross, Ryan Thomas

机构信息

Department of Anaesthesia, St James's Hospital, Dublin, Ireland.

出版信息

Crit Care Med. 2006 Aug;34(8):2134-9. doi: 10.1097/01.CCM.0000227647.77356.AB.

Abstract

OBJECTIVE

Cytokine response after cardiac surgery may be genetically influenced. A study was carried out to investigate the relation between cytokine gene expression in peripheral blood mononuclear cells, genotype, and clinical events after cardiac surgery.

DESIGN

A case-control study was performed.

SETTING

Cardiac intensive care unit in a university hospital.

SUBJECTS

A total of 82 patients having elective cardiac surgery were divided into those having uncomplicated recovery (n = 48) or recovery complicated by hyperlactatemia or requirement for inotropic support (n = 34).

INTERVENTIONS

The relative change in peripheral blood mononuclear cell tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) messenger RNA 1 and 6 hrs after cardiopulmonary bypass was compared with a baseline preoperative level using quantitative reverse transcriptase polymerase chain reaction. DNA was analyzed for carriage of TNF-alpha and IL-10 polymorphic alleles.

MEASUREMENTS AND MAIN RESULTS

Cardiopulmonary bypass was longer in duration in the complicated group. TNF-alpha gene expression decreased and IL-10 gene expression increased in peripheral blood mononuclear cells after surgery when compared with preoperative levels. One hour after cardiopulmonary bypass, the complicated group had more TNF-alpha and less IL-10 messenger RNA production than the uncomplicated group. The IL-10/TNF-alpha ratio was greater in uncomplicated than in complicated recovery patients. An IL-10 haplotype was identified that was less frequent in the complicated group. There was no difference between groups in TNF-alpha genotype. On multivariate analysis, cardiopulmonary bypass time and the IL-10/TNF-alpha messenger RNA ratio were independent predictors of outcome.

CONCLUSIONS

There is a predominant anti-inflammatory cytokine response after uneventful cardiac surgery. IL-10 may have a protective role after cardiac surgery.

摘要

目的

心脏手术后的细胞因子反应可能受基因影响。开展一项研究以调查心脏手术后外周血单个核细胞中细胞因子基因表达、基因型与临床事件之间的关系。

设计

进行一项病例对照研究。

地点

一所大学医院的心脏重症监护病房。

研究对象

总共82例行择期心脏手术的患者被分为恢复过程无并发症组(n = 48)和恢复过程并发高乳酸血症或需要使用血管活性药物支持组(n = 34)。

干预措施

使用定量逆转录聚合酶链反应,将体外循环后1小时和6小时外周血单个核细胞肿瘤坏死因子-α(TNF-α)和白细胞介素-10(IL-10)信使核糖核酸的相对变化与术前基线水平进行比较。分析DNA中TNF-α和IL-10多态性等位基因的携带情况。

测量指标及主要结果

并发症组的体外循环时间更长。与术前水平相比,术后外周血单个核细胞中TNF-α基因表达降低,IL-10基因表达增加。体外循环1小时后,并发症组产生的TNF-α比无并发症组多,IL-10信使核糖核酸比无并发症组少。无并发症恢复患者的IL-10/TNF-α比值高于并发症恢复患者。在并发症组中发现一种频率较低的IL-10单倍型。两组之间的TNF-α基因型无差异。多因素分析显示,体外循环时间和IL-10/TNF-α信使核糖核酸比值是预后的独立预测因素。

结论

心脏手术顺利完成后存在主要的抗炎细胞因子反应。IL-10可能在心脏手术后起到保护作用。

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