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脓毒症患者循环内皮祖细胞增加:与生存率的相关性

Increased circulating endothelial progenitor cells in septic patients: correlation with survival.

作者信息

Rafat Neysan, Hanusch Christine, Brinkkoetter Paul T, Schulte Jutta, Brade Joachim, Zijlstra Jan G, van der Woude Fokko J, van Ackern Klaus, Yard Benito A, Beck Grietje Ch

机构信息

Department of Anaesthesiology and Critical Care Medicine, University of Heidelberg, Germany.

出版信息

Crit Care Med. 2007 Jul;35(7):1677-84. doi: 10.1097/01.CCM.0000269034.86817.59.

Abstract

OBJECTIVE

Endothelial damage and detachment of endothelial cells are known to occur in septic patients. Thus, recruitment of circulating endothelial progenitor cells (cEPCs) to these lesions might have a beneficial effect on the clinical course in septic patients. Therefore, we were interested in whether EPCs, detected by flow cytometry, are increasingly mobilized during sepsis and if this mobilization is associated with clinical outcome.

DESIGN

Prospective, nonrandomized study.

SETTING

Intensive care unit of a university hospital.

PATIENTS

Patients with (n = 32) and without (n = 15) sepsis and healthy volunteers (n = 15).

INTERVENTIONS

Peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation, and cEPCs were characterized by three-color fluorescence flow cytometry using antibodies against CD133, CD34, and vascular endothelial growth factor receptor-2. Serum concentrations of vascular endothelial growth factor, granulocyte macrophage-colony stimulating factor, and erythropoietin were determined by enzyme-linked immunosorbent assay. Severity of sepsis was assessed according to Acute Physiology and Chronic Health Evaluation II scoring.

MEASUREMENTS AND MAIN RESULTS

In septic patients, the number of cEPCs was significantly higher than in nonseptic intensive care unit patients (p < .05) and healthy controls (p < .02). Nonsurvivors (n = 8), defined as death within 28 days after onset of sepsis, had significantly lower numbers of cEPCs than survivors (n = 24) (p < .0001). The number of cEPCs was correlated with survival in septic patients. Serum vascular endothelial growth factor concentrations were significantly higher in septic patients compared with nonseptic intensive care unit patients and healthy controls (p < .01) and correlated with the cEPC numbers (p < .0001). Similar findings were observed for granulocyte macrophage-colony stimulating factor and erythropoietin.

CONCLUSIONS

Our data suggest that cEPC enumeration in peripheral blood of septic patients might be a valuable marker to assess the clinical outcome in these patients.

摘要

目的

已知脓毒症患者会发生内皮损伤和内皮细胞脱离。因此,循环内皮祖细胞(cEPCs)募集至这些损伤部位可能对脓毒症患者的临床病程产生有益影响。所以,我们感兴趣的是通过流式细胞术检测到的EPCs在脓毒症期间是否会被更多地动员起来,以及这种动员是否与临床结局相关。

设计

前瞻性、非随机研究。

地点

大学医院重症监护病房。

患者

脓毒症患者(n = 32)、非脓毒症患者(n = 15)和健康志愿者(n = 15)。

干预措施

通过Ficoll密度梯度离心法分离外周血单个核细胞,使用抗CD133、CD34和血管内皮生长因子受体-2的抗体,通过三色荧光流式细胞术对cEPCs进行鉴定。采用酶联免疫吸附测定法测定血清血管内皮生长因子、粒细胞巨噬细胞集落刺激因子和促红细胞生成素的浓度。根据急性生理学与慢性健康状况评分系统II对脓毒症严重程度进行评估。

测量指标及主要结果

脓毒症患者的cEPCs数量显著高于非脓毒症重症监护病房患者(p < 0.05)和健康对照者(p < 0.02)。脓毒症发病后28天内死亡的非存活者(n = 8)的cEPCs数量显著低于存活者(n = 24)(p < 0.0001)。脓毒症患者的cEPCs数量与生存率相关。与非脓毒症重症监护病房患者和健康对照者相比,脓毒症患者的血清血管内皮生长因子浓度显著更高(p < 0.01),且与cEPCs数量相关(p < 0.0001)。粒细胞巨噬细胞集落刺激因子和促红细胞生成素也有类似发现。

结论

我们的数据表明,脓毒症患者外周血中cEPCs计数可能是评估这些患者临床结局的一个有价值的指标。

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