循环miR-126表达水平与脓毒症患者发生ARDS的风险及脓毒症严重程度和预后的关联

Correlation among expression level of circulating miR-126，risk of acute respiratory distress syndrome，and septic severity and prognosis in patients with sepsis

摘要:

目的：评估血浆微小RNA（microRNA，miR）-126表达水平对脓毒症患者急性呼吸窘迫综合征（acute respiratory distress syndrome，ARDS）发生风险的预测作用，及其与脓毒症疾病严重程度、炎症水平和患者预后的关联。方法：连续纳入172例脓毒症患者。患者入院24 h内采集外周血并分离血浆，采用定量聚合酶链式反应检测血浆miR-126表达水平。采用酶联免疫吸附试验检测血浆炎症因子[包括肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白介素（interleukin，IL）-1β、IL-6 和IL-17]表达量。同时记录患者28 d死亡率。结果：住院期间共50例（30.8%）患者发生ARDS，血浆miR-126在ARDS患者中的表达水平明显高于非ARDS患者（P<0.001）。受试者工作特征曲线（receiver-operating characteristic，ROC）分析显示，血浆miR-126表达水平可以区分ARDS患者和非ARDS患者，其曲线下面积（area under the ROC，AUC）为0.741（95%CI=0.666~0.815）。多元逻辑回归分析显示，miR-126高表达（P<0.001）是较高ARDS发病风险的独立预测因素。在总体脓毒症患者中，血浆miR-126表达量与血清肌酐（P=0.004）、C反应蛋白（P<0.001）、降钙素原（P<0.001）、急性生理功能和慢性健康状况II评分（P<0.001）、序贯器官衰竭（sequential organ failure assessment，SOFA）评分（P<0.001），以及炎性因子TNF-α（P=0.001）、IL-1β（P=0.002）、IL-6（P=0.011）和IL-17（P=0.002）水平均成正相关。此外，血浆miR-126在死亡患者中的表达量明显高于生存患者（P<0.001），ROC曲线分析显示其可以预测脓毒症患者较高的28 d死亡风险，AUC为0.686（95%CI=0.601~0.771）。结论：本研究表明，较高的循环miR-126表达量可以预测脓毒症患者中较高的ARDS发病率，并且可以作为辅助脓毒症疾病监测和患者预后的生物标志物。

Abstract:

Objective：To assess the predictive role of plasma microRNA（miR）-126 on risk of acute respiratory distress syndrome （ARDS） in patients with sepsis，and to investigate the correlation of miR-126 and sepsis severity，inflammation level and prognosis. Methods：A total of 172 patients with sepsis were continuously enrolled. Peripheral blood samples of patients were collected within 24 hours after admission，and plasma was separated；expression level of miR-126 was detected by quantitive polymerase chain reaction. Expression levels of inflammatory cytokines[including tumor necrosis factor-α（TNF-α），interleukin（IL）-1β，IL-6 and IL-17） in plasma were detected by enzyme-linked immune sorbent assay（ELISA）. Meanwhile，the 28-day mortality was recorded as well. Results：Among them，50 patients（30.8%） had ARDS during hospitalization，and plasma miR-126 expression was significantly elevated in ARDS patients when compared with non-ARDS patients（P<0.001）. According to the receiver operating characteristic curve（ROC） analysis，expression level of plasma miR-126 was able to differentiate ARDS patients form non-ARDS patients，with area under the ROC（AUC） of 0.741（95%CI=0.666-0.815）. In accordance with the multivariate logistic regression model analysis，high expression of miR-126（P<0.001） was the independent predictive factor for relative-high onset-risk of ARDS. In addition，of all sepsis patients，plasma miR-126 expression was positively correlated with levels of serum creatinine（P=0.004），C reactive protein（P<0.001），procal－citonin（P<0.001），acute physiology and chronic health evaluation Ⅱ（APACHE Ⅱ） score（P<0.001），sequential organ failure as－sessment（SOFA） score（P<0.001），and inflammatory factors of TNF-α（P=0.001），IL-1β（P=0.002），IL-6（P=0.011） and IL-17（P=0.002）. Moreover，the expression level of plasma miR-126 in the dead was significantly higher than that in the survivors（P<0.001）. According to the ROC curve analysis，it was able to predict that patients with sepsis had a high 28-day mortality risk，with AUC of 0.686（95%CI=0.601-0.771）. Conclusion：Higher circulating miR-126 expression can predict the higher ARDS in－cidence in patients with sepsis，and can serve as a biomarker for disease surveillance and patients’ prognosis in sepsis.