循环miR-126表达水平与脓毒症患者发生急性呼吸窘迫综合征风险以及脓毒症疾病严重程度和预后的关联

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

摘要:

目的 本研究旨在评估血浆微小RNA(microRNA, miR)-126表达水平对脓毒症患者中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 研究连续纳入172例脓毒症患者。于患者入院24小时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, TNF-α)、白介素(interleukin, IL)-1β、IL-6 和IL-17)表达量。同时记录患者28天死亡率。结果 住院期间共50例(30.8%)患者发生ARDS，血浆miR-126在ARDS患者中的表达水平显著高于非ARDS患者(P<0.001)，且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%置信区间: 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)水平均正相关。此外，血浆miR-126在死亡患者中的表达量显著高于生存患者(P<0.001)，ROC曲线分析显示其可以预测脓毒症患者较高的28天死亡风险，AUC为0.686(95%置信区间：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 This study aimed to assess the correlation of plasma miR-126 with the risk of acute respiratory distress syndrome (ARDS), severity, inflammation level and prognosis in sepsis patients. Methods One hundred and seventy-two sepsis patients were enrolled in this study. The peripheral blood samples of patients were collected within 24 hours after hospital admission, and plasma was separated for miR-126 expression detection by quantitive polymerase chain reaction. The expressions of inflammatory cytokines (including TNF-α, IL-1β, IL-6 and IL-17) levels in plasma were evaluated by enzyme-linked immuno sorbent assay (ELISA). Meanwhile, the 28-day mortality was recorded as well. Results There were 50 (30.8%) patients who had ARDS during hospitalization, and plasma miR-126 expression was elevated in ARDS patients compared with non-ARDS patients (P<0.001), and it could differentiate ARDS patients form non-ARDS patients with AUC of 0.741 (95%CI: 0.666-0.815) according to the receiver operating characteristic curve (ROC) analysis. The multivariate logistic regression model analysis revealed that plasma miR-126 (high vs. low) independently predicted higher risk of ARDS (P<0.001). In addition, in the total sepsis patients, plasma miR-126 expression was positively correlated with levels of Scr (P=0.004), CRP (P<0.001), PCT (P<0.001), APACHE II score (P<0.001), SOFA score (P<0.001), and TNF-α (P=0.001), IL-1β (P=0.002), IL-6 (P=0.011) as well as IL-17 (P=0.002) expressions in plasma. Moreover, the plasma miR-126 was upregulated in non-survivors compared with that in survivors (P<0.001), ROC curve analysis revealed that it could distinguish survivors form the non-survivors with AUC of 0.686 (95%CI: 0.601-0.771). Conclusion Higher circulating miR-126 expression is correlated with higher risk of ARDS and could serve as a biomarker for disease surveillance and prognosis in sepsis.