Correlation and clinical significance of miR-128-3p and TLR4 expression in peripheral blood mononuclear cells of patients with AECOPD
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摘要: 目的 研究慢性阻塞性肺疾病急性加重期(AECOPD)患者外周血单个核细胞(PBMCs)中微小RNA(miR)-128-3p、Toll样受体4(TLR4)表达的相关性及临床意义。方法 选择2020年1月-2022年2月期间在我科住院治疗的122例AECOPD患者作为AECOPD组，在我科门诊就诊的140例稳定期COPD患者作为稳定期COPD组，在我院体检的110例志愿者作为对照组。检测PBMCs中miR-128-3p、TLR4的mRNA表达水平及实验室指标白细胞计数(WBC)、超敏C反应蛋白(hs-CRP)、血沉(ESR)，评价AECOPD患者的短期预后、结局包括存活和死亡。结果 AECOPD组PBMCs中miR-128-3p、TLR4的mRNA表达水平及WBC、hs-CRP、ESR水平均高于稳定期COPD组和对照组(P< 0.05); AECOPD组PBMCs中miR-128-3p、TLR4的mRNA表达水平呈正相关，miR-128-3p、TLR4的mRNA表达水平与WBC、hs-CRP、ESR水平呈正相关; AECOPD组中死亡患者PBMCs中miR-128-3p、TLR4的mRNA表达水平高于存活患者(P< 0.05)，WBC、hs-CRP、ESR水平与存活患者比较均差异无统计学意义(P>0.05); 经ROC曲线分析，PBMCs中miR-128-3p、TLR4的mRNA表达水平能区别AECOPD与稳定期COPD、预测AECOPD患者的预后。结论 AECOPD患者PBMCs中miR-128-3p、TLR4的表达上调且具有正相关关系，两者共同参与AECOPD的病情加重及预后恶化。
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关键词:
- 慢性阻塞性肺疾病急性加重期 /
- 微小RNA-128-3p /
- Toll样受体4 /
- 预后
Abstract: Objective To study the correlation and clinical significance of the expression of microRNA(miR) -128-3p and toll like receptor 4(TLR4) in peripheral blood mononuclear cells(PBMCs) of patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods One hundred and twenty-two patients with AECOPD hospitalized in our department from January 2020 to February 2022 were selected as AECOPD group, 140 patients with stable COPD treated in our outpatient department as stable COPD group, and 110 volunteers examined in our hospital as control group. The mRNA expression levels of miR-128-3p and TLR4 in PBMCs and laboratory indexes such as white blood cell count(WBC), high-sensitivity C-reactive protein(hs-CRP) and erythrocyte sedimentation rate(ESR) were detected. The short-term prognosis of AECOPD patients was evaluated and the outcome including survival and death.Results The mRNA expression levels of miR-128-3p and TLR4 in PBMCs and the levels of WBC, hs-CRP and ESR of AECOPD group were higher than those in stable COPD group and control group(P< 0.05). In AECOPD group, the mRNA expression levels of miR-128-3p and TLR4 in PBMCs were positively correlated, and the mRNA expression levels of miR-128-3p and TLR4 were positively correlated with the levels of WBC, hs-CRP and ESR. In AECOPD group, the mRNA expression levels of miR-128-3p and TLR4 in PBMCs of dead patients were higher than those of surviving patients(P< 0.05), and there was no difference of WBC, hs-CRP and ESR between dead patients and surviving patients(P>0.05). By ROC curve analysis, the mRNA expression levels of miR-128-3p and TLR4 in peripheral blood can distinguish AECOPD from stable COPD and predict the prognosis of AECOPD patients.Conclusion The expressions of miR-128-3p and TLR4 in PBMCs of patients with AECOPD are up-regulated and positively correlated. Both of them are involved in the aggravation of AECOPD and the deterioration of prognosis. -
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表 1 3组间一般资料的比较
X±S 组别 例数 性别/例 年龄/岁 吸烟史/例(%) BMI 男 女 AECOPD组 122 72 50 64.24±11.03 58(47.54) 22.01±5.12 稳定期COPD组 140 79 61 62.85±12.08 61(43.57) 22.77±6.09 对照组 110 60 50 60.78±10.77 45(40.91) 22.26±4.85 F 0.479 2.703 1.056 0.670 P 0.787 0.068 0.590 0.512 
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表 2 3组PBMCs中miR-128-3p、TLR4表达水平的比较
X±S 组别 例数 miR-128-3p TLR4 AECOPD组 122 1.69±0.49 1.77±0.41 稳定期COPD组 140 1.23±0.40 1.38±0.39 对照组 110 1.00±0.24 1.00±0.27
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表 3 PBMCs中miR-128-3p、TLR4区分AECOPD与稳定期COPD的ROC曲线分析
指标 曲线下面积 95%CI P 最佳截取值 灵敏度/% 特异度/% miR-128-3p 0.759 0.701~0.818 < 0.001 1.507 77.86 64.75 TLR4 0.751 0.695~0.811 < 0.001 1.649 73.57 63.11
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表 4 3组WBC、hs-CRP、ESR水平的比较
X±S 组别 例数 WBC/(×109·L-1) hs-CRP/(mg·L-1) ESR/(mm·h-1) AECOPD组 122 17.82±3.571)2) 37.59±8.941)2) 71.38±11.851)2) 稳定期COPD组 140 8.59±1.47 5.49±1.04 11.75±2.42 对照组 110 7.86±1.25 5.15±0.95 8.58±1.85 与对照组比较，1)P < 0.05; 与稳定期COPD组比较，2)P < 0.05。
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表 5 AECOPD组患者miR-128-3p、TLR4与WBC、hs-CRP、ESR的相关性
指标 miR-128-3p TLR4 r P r P WBC 0.329 < 0.001 0.241 0.001 hs-CRP 0.221 0.003 0.293 < 0.001 ESR 0.287 < 0.001 0.209 0.008
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表 6 AECOPD组中死亡患者与存活患者miR-128-3p、TLR4、WBC、hs-CRP、ESR的比较
X±S 结局 例数 miR-128-3p TLR4 WBC/(×109·L-1) hs-CRP/(mg·L-1) ESR/(mm·h-1) 死亡 12 2.07±0.29 2.03±0.17 18.24±7.41 38.16±10.24 72.94±13.57 存活 110 1.64±0.49 1.74±0.42 17.77±3.41 37.53±8.16 71.21±11.24 t 2.977 2.364 0.391 0.248 0.496 P 0.004 0.020 0.696 0.805 0.621
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表 7 PBMCs中miR-128-3p、TLR4预测AECOPD患者死亡的ROC曲线分析
指标 曲线下面积 95%CI P 最佳截取值 灵敏度/% 特异度/% miR-128-3p 0.772 0.660~0.883 0.002 1.863 63.64 75.00 TLR4 0.749 0.653~0.846 0.005 2.036 75.45 66.67
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