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  • 王华,王莉,郭东风.脓毒症患者血浆微RNA-146a表达与患病风险、炎性因子水平及预后的相关性分析[J].第二军医大学学报,2020,41(2):135-140    [点击复制]
  • WANG Hua,WANG Li,GUO Dong-feng.Correlation analysis of plasma microRNA-146a with risk, inflammatory cytokine levels and prognosis in sepsis patients[J].Acad J Sec Mil Med Univ,2020,41(2):135-140   [点击复制]
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脓毒症患者血浆微RNA-146a表达与患病风险、炎性因子水平及预后的相关性分析
王华1,王莉2,郭东风1*
0
(1. 海军军医大学(第二军医大学)附属公利医院急诊科, 上海 200135;
2. 上海中医药大学附属第七人民医院皮肤科, 上海 200137
*通信作者)
摘要:
目的 评估脓毒症患者血浆miRNA-146a表达水平对患病风险及预后的价值。方法 连续纳入2015年10月至2017年3月于海军军医大学(第二军医大学)附属公利医院急诊科和ICU就诊的132例脓毒症患者,以及同期在健康体检中心进行健康体检的131名健康对照。采集两组研究对象的血液样本,采用qRT-PCR检测血浆miRNA-146a表达,采用ELISA法测定血清炎性因子(CRP、TNF-α、IL-1β、IL-6、IL-8、IL-10)水平。结果 与健康对照相比,脓毒症患者血浆中miRNA-146a表达水平较低(Z=-7.423,P<0.01);ROC曲线显示血浆miRNA-146a对脓毒症有较好的诊断价值,AUC为0.765(95% CI 0.707~0.823),取约登指数最大值处的界值为最佳诊断界值,此时灵敏度和特异度分别为87.9%和61.8%。多元logistic回归模型显示血浆miRNA-146a表达水平低是脓毒症患病风险的独立预测因素(OR=0.312,95% CI 0.225~0.434,P<0.01)。Spearman相关分析显示血浆miRNA-146a表达水平与急性生理功能和慢性健康状况Ⅱ(APACHE Ⅱ)评分呈负相关(r=-0.562,P<0.01),与血清CRP(r=-0.304,P<0.001)、TNF-α(r=-0.287,P=0.001)、IL-1β(r=-0.173,P=0.047)及IL-6(r=-0.213,P=0.014)呈负相关,与血清IL-10(r=0.225,P=0.009)呈正相关。与存活脓毒症患者相比,死亡患者血浆中miRNA-146a的表达水平降低(Z=-2.818,P=0.005)。ROC曲线分析显示血浆miRNA-146a对脓毒症有良好的预后价值,AUC为0.660(95% CI 0.546~0.773),最佳诊断界值的灵敏度和特异度分别为88.5%和47.2%。结论 血浆miRNA-146a表达水平低是脓毒症患病的独立预测因素,并与疾病严重程度高、炎性因子水平高及预后不良有关。
关键词:  微RNA-146a  脓毒症  危险因素  预后  炎性因子
DOI:10.16781/j.0258-879x.2020.02.0135
投稿时间:2019-06-27修订日期:2019-09-11
基金项目:
Correlation analysis of plasma microRNA-146a with risk, inflammatory cytokine levels and prognosis in sepsis patients
WANG Hua1,WANG Li2,GUO Dong-feng1*
(1. Department of Emergency, Gongli Hospital, Naval Medical University(Second Military Medical University), Shanghai 200135, China;
2. Department of Dermatology, Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China
*Corresponding author)
Abstract:
Objective To evaluate the role of plasma microRNA-146a (miRNA-146a) in risk prediction and prognosis of the sepsis. Methods A total of 132 sepsis patients admitted to Department of Emergency and Intensive Care Unit (ICU) of Gongli Hospital affiliated to Naval Medical University (Second Military Medical University) between October 2015 and March 2017 and 131 healthy controls were consecutively enrolled in this study. Blood samples from septic patients and healthy controls were collected. Plasma miRNA-146a expression was detected by qRT-PCR. Serum inflammatory cytokines (C-reactive protein[CRP], tumor necrosis factor α[TNF-α], interleukin[IL]-1β, IL-6, IL-8 and IL-10) were detected by enzyme-linked immunosorbent assay (ELISA). Results Low expression of plasma miRNA-146a was found in sepsis patients compared to healthy controls (Z=-7.423, P<0.01). Receiver operating characteristic (ROC) curve revealed that plasma miRNA-146a disclosed a good diagnostic value for sepsis, with an area under curve (AUC) of 0.765 (95% confidence interval[CI] 0.707-0.823); sensitivity and specificity were 87.9% and 61.8% at the best cut-off point, respectively. Multivariate logistic analysis indicated that low plasma miRNA-146a expression was an independent predictive factor for sepsis (odds ratio[OR]=0.312, 95% CI 0.225-0.434, P<0.01). Spearman correlation showed that miRNA-146a expression was negatively correlated with acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score (r=-0.562, P<0.01), CRP (r=-0.304, P<0.001), TNF-α (r=-0.287, P=0.001), IL-1β (r=-0.173, P=0.047) and IL-6 (r=-0.213, P=0.014), while it was positively correlated with IL-10 (r=0.225, P=0.009). miRNA-146a expression in plasma of non-survivors was lower than that in survivors (Z=-2.818, P=0.005). ROC curve revealed that plasma miRNA-146a had a good prognostic value for sepsis, with AUC being 0.660 (95% CI 0.546-0.773), and the sensitivity and specificity were 88.5% and 47.2% at the best cut-off point, respectively. Conclusion Low expression of plasma miRNA-146a is an independent predictive factor for sepsis, and it is correlated with high severity of the disease, high levels of inflammatory cytokine, and poor prognosis.
Key words:  microRNA-146a  sepsis  risk factors  prognosis  inflammatory cytokine