Gene expression changes in the human diaphragm after cardiothoracic surgery
Gene expression changes in the human diaphragm after cardiothoracic surgery
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DOI：
10.1016/j.jtcvs.2011.02.025
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发表时间：
2011-11-01
影响因子：
6
通讯作者：
Martin, A. Daniel
中科院分区：
文献类型：
--
作者：
Huang, Tseng-Tien;Deoghare, Harsha V.;Martin, A. Daniel
目的：探讨心胸手术(体外循环和控制性机械通气)对人膈肌信使RNA基因表达的影响。我们假设负责应激反应、氧化还原调节、蛋白质代谢、能量代谢和收缩功能的基因可能会在心胸手术中发生改变。方法：5例男性患者(67+/-11岁)在心胸手术中获得成对的横隔膜活检标本，第一个样本在横隔膜暴露时立即获得，第二个样本在手术中尽可能晚(样本之间的间隔4.9+/-1.8小时)。我们用微阵列分析了5对标本的信使RNA(Hu U133 plus 2.0；Affymetrix UK Ltd，High Wycombe，UK)。用定量逆转录聚合酶链式反应对一组差异表达的基因进行验证。结果：微阵列分析鉴定出779个差异表达的独特基因产物(早期样本和晚期样本)(P<；.005)。术后应激反应和氧化还原调节相关基因表达上调。此外，我们发现组织蛋白酶C(2.7倍)、组织蛋白酶L1(2.0倍)、各种泛素结合酶(E2，约1.8倍)、促炎细胞因子白细胞介素6(15.6倍)和肌肉特异性泛素连接酶(MURF-1，2.6倍)的表达显著上调。定量逆转录聚合酶链式反应和基因芯片的倍增变化值之间存在显著的相关性(r=0.95，P<；0.0001)。结论：心胸外科手术后人体横隔膜基因的表达发生了快速变化，包括与应激反应、炎症反应、氧化还原调节和蛋白降解相关的基因。这些结果可能为长期心胸手术后的横隔肌生物学提供更深入的了解。(《胸心外科杂志》2011；142：1214-22)
Objective: We examined the effects of cardiothoracic surgery, including cardiopulmonary bypass and controlled mechanical ventilation, on messenger RNA gene expression in human diaphragm. We hypothesized that genes responsible for stress response, redox regulation, protein turnover, energy metabolism, and contractile function would be altered by cardiothoracic surgery.Methods: Paired diaphragm biopsy samples were obtained from 5 male patients (67 +/- 11 years) during cardiothoracic surgery, the first as soon as the diaphragm was exposed and the second as late in surgery as possible (4.9 +/- 1.8 hours between samples). We profiled messenger RNA from 5 specimen pairs with microarray analysis (Hu U133 plus 2.0; Affymetrix UK Ltd, High Wycombe, UK). Quantitative reverse transcriptase polymerase chain reaction was performed with a select set of genes exhibiting differential expression for validation.Results: Microarray analysis identified 779 differentially expressed (early vs late samples) unique gene products (P < .005). Postoperatively, genes related to stress response and redox regulation were upregulated. Additionally, we found significantly upregulated expression of cathepsin C (2.7-fold), cathepsin L1 (2.0-fold), various ubiquitin-conjugating enzymes (E2, approximately 1.8-fold), proinflammatory cytokine interleukin 6 (15.6-fold), and muscle-specific ubiquitin ligase (MuRF-1, 2.6-fold). Comparison of fold change values obtained by quantitative reverse transcriptase polymerase chain reaction and microarray yielded significant correlation (r = 0.95, P < .0001).Conclusions: Cardiothoracic surgery results in rapid changes in human diaphragm gene expression in the operating room, including genes related to stress response, inflammation, redox regulation, and proteolysis. These results may provide insight into diaphragm muscle biology after prolonged cardiothoracic procedures. (J Thorac Cardiovasc Surg 2011;142:1214-22)