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出血及随后的异体红细胞输注与多发伤患者特征性单核细胞信使核糖核酸表达模式相关——全基因组视角

Hemorrhage and subsequent allogenic red blood cell transfusion are associated with characteristic monocyte messenger RNA expression patterns in patients after multiple injury-a genome wide view.

作者信息

Bogner Viktoria, Baker Henry V, Kanz Karl-Georg, Moldawer L L, Mutschler Wolf, Biberthaler Peter

机构信息

Chirurgische Klinik und Poliklinik-Innenstadt, Ludwig-Maximilians University, Munich, Munich, Germany.

出版信息

J Trauma. 2009 Oct;67(4):792-801. doi: 10.1097/TA.0b013e31819d9c04.

Abstract

INTRODUCTION

As outcome to severe trauma is frequently affected by massive blood loss and consecutive hemorrhagic shock, replacement of red blood cell (RBC) units remains indispensable. Administration of RBC units is an independent risk factor for adverse outcome in patients with trauma. The impact of massive blood transfusion or uncrossmatched blood transfusion on the patients' immune response in the early posttraumatic period remains unclear.

MATERIAL

Thirteen patients presenting with blunt multiple injuries (Injury Severity Score >16) were studied. Monocytes were obtained on admission and at 6, 12, 24, 48, and 72 hours after trauma. Biotinylated complementary RNA targets were hybridized to Affymetrix HG U 133A microarrays. The data were analyzed by a supervised analysis based on whether the patients received massive blood transfusions, and then subsequently, by hierarchical clustering, and by Ingenuity pathway analysis.

RESULTS

Supervised analysis identified 224 probe sets to be differentially expressed (p < 0.001) in patients who received massive blood transfusion, when compared with those who did not. In addition, 331 probe sets were found differentially expressed (p < 0.001) in patients who received uncrossmatched RBC units in comparison with those who exclusively gained crossmatched ones. Functional pathway analysis of the respectively identified gene expression profiles suggests a contributory role by the AKT/PI3Kinase pathway, the mitogen-activated protein-kinase pathway, the Ubiquitin pathway, and the diverse inflammatory networks.

CONCLUSION

We exhibited for the first time a serial, sequential screening analysis of monocyte messenger RNA expression patterns in patients with multiple trauma indicating a strongly significant association between the patients' genomic response in blood monocytes and massive or uncrossmatched RBC substitution.

摘要

引言

由于严重创伤的预后常受大量失血和连续性失血性休克影响,红细胞(RBC)单位的补充仍然必不可少。输注RBC单位是创伤患者不良预后的独立危险因素。大量输血或未交叉配血输血对创伤后早期患者免疫反应的影响尚不清楚。

材料

研究了13例钝性多发伤患者(损伤严重度评分>16)。在入院时以及创伤后6、12、24、48和72小时获取单核细胞。将生物素化的互补RNA靶标与Affymetrix HG U 133A微阵列杂交。基于患者是否接受大量输血进行监督分析,随后通过层次聚类和 Ingenuity 通路分析对数据进行分析。

结果

监督分析确定,与未接受大量输血的患者相比,接受大量输血的患者中有224个探针集差异表达(p<0.001)。此外,与仅接受交叉配血红细胞单位的患者相比,接受未交叉配血红细胞单位的患者中有331个探针集差异表达(p<0.001)。对分别鉴定出的基因表达谱进行功能通路分析表明,AKT/PI3激酶通路、丝裂原活化蛋白激酶通路、泛素通路和多种炎症网络起了作用。

结论

我们首次对多发伤患者的单核细胞信使RNA表达模式进行了系列、连续的筛选分析,表明患者血液单核细胞中的基因组反应与大量或未交叉配血的红细胞替代之间存在高度显著的关联。

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