血清miR-212-5p、miR-221-3p与AECOPD患者TLR4/NF-κB炎症信号通路和预后的关系研究

Study on the relationship of serum miR-212-5p,miR-221-3p with TLR4/NF-κB inflammatory signaling pathway and prognosis of patients with AECOPD

目的探讨血清微小核糖核酸(miRNA)-212-5p(miR-212-5p)、miRNA-221-3p(miR-221-3p)与慢性阻塞性肺疾病(COPD)急性加重期(AECOPD)患者Toll样受体4(TLR4)/核因子κB(NF-κB)炎症信号通路和预后的关系。方法选取2020年1月至2022年12月聊城市第二人民医院收治的298例COPD患者为研究对象,其中AECOPD患者175例(AECOPD组),COPD稳定期患者123例(COPD稳定期组),另纳入同期在该院体检健康者100例作为健康对照组。根据28 d预后情况,将AECOPD患者分为预后良好组和预后不良组。采用荧光定量聚合酶链反应检测血清miR-212-5p、miR-221-3p及TLR4/NF-κB信号通路相关指标的水平。采用Pearson相关分析AECOPD患者血清miR-212-5p、miR-221-3p水平与TLR4/NF-κB信号通路相关指标水平的相关性。采用多因素Logistic回归分析AECOPD患者预后不良的影响因素。绘制受试者工作特征(ROC)曲线分析miR-212-5p、miR-221-3p水平对AECOPD患者预后不良的预测价值。结果COPD稳定期组、AECOPD组血清TLR4 mRNA、NF-κB信使RNA(mRNA)水平高于健康对照组,血清miR-212-5p、miR-221-3p水平低于健康对照组,差异均有统计学意义(P<0.05);AECOPD组血清TLR4 mRNA、NF-κB mRNA水平高于COPD稳定期组,血清miR-212-5p、miR-221-3p水平低于COPD稳定期组,差异均有统计学意义(P<0.05)。随访28 d,AECOPD患者中预后不良62例(预后不良组),预后良好113例(预后良好组)。预后良好组血清miR-212-5p、miR-221-3p水平高于预后不良组,而血清TLR4 mRNA、NF-κB mRNA水平低于预后不良组,差异均有统计学意义(P<0.05)。Pearson相关性分析结果显示,AECOPD患者血清miR-212-5p、miR-221-3p水平与TLR4 mRNA、NF-κB mRNA水平均呈负相关(P<0.05)。预后良好组血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平低于预后不良组,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,IL-6、TNF-α、TLR4 mRNA和NF-κB mRNA水平升高是AECOPD患者预后不良的危险因素(P<0.05),miR-212-5p、miR-221-3p水平升高是AECOPD患者预后不良的保护因素(P<0.05)。ROC曲线分析结果显示,血清miR-212-5p、miR-221-3p联合预测AECOPD预后不良的曲线下面积(AUC)为0.862,明显高于miR-212-5p、miR-221-3p单独预测的0.722、0.755(P<0.05)。结论AECOPD预后不良患者血清miR-212-5p、miR-221-3p水平下调可能与调节TLR4/NF-κB炎症信号通路有关,且miR-212-5p、miR-221-3p联合检测对AECOPD患者的预后不良具有较高的预测价值。

Objective To explore the relationship of serum microribonucleic acid(miRNA)-212-5p(miR-212-5p),miRNA-221-3p(miR-221-3p)with Toll like receptor 4(TLR4)/nuclear factorκB(NF-κB)inflammatory signaling pathway and prognosis of patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods A total of 298 patients with chronic obstructive pulmonary disease(COPD),who were admitted to Liaocheng Second People′s Hospital from January 2020 to December 2022,were selected,including 175 patients with AECOPD(AECOPD group)and 123 patients with stable COPD(stable COPD group),while 100 healthy individuals underwent physical examination in the hospital during the same period were included as healthy control group.AECOPD patients was divided into good prognosis group and poor prognosis group based on the prognosis within 28 d.The expression levels of serum miR-212-5p,miR-221-3p and TLR4/NF-κB signaling pathway related indicators were detected by fluorescence quantitative polymerase chain reaction.The correlation between the expression levels of serum miR-212-5p,miR-221-3p with TLR4/NF-κB signaling pathway related indicators of patients with AECOPD was analyzed by the Pearson′s correlation analysis.The influencing factors affected the poor prognosis of patients with AECOPD were analyzed by the multivariate Logistic regression.The predictive value of expression levels of miR-212-5p and miR-221-3p for the prognosis of patients with AECOPD was analyzed by the receiver operating characteristic(ROC)curve.Results The levels of serum TLR4 mRNA and NF-κB mRNA in the stable COPD group and the AECOPD group were higher than those in the healthy control group,and the levels of serum miR-212-5p and miR-221-3p were lower than those in the healthy control group,with statistically significant differences(P<0.05).The levels of serum TLR4 mRNA and NF-κB mRNA in the AECOPD group were higher than those in the stable COPD group,and the levels of serum miR-212-5p and miR-221-3p were lower than those in the stable COPD group,with statistically significant differences(P<0.05).After 28 d of follow-up,62 cases of AECOPD patients had a poor prognosis(poor prognosis group)and 113 cases had a good prognosis(good prognosis group).The levels of serum miR-212-5p and miR-221-3p in the good prognosis group were higher than those in poor prognosis group,and the levels of serum TLR4 mRNA and NF-κB mRNA were lower than those in the poor prognosis group,with statistically significant differences(P<0.05).Pearson′s correlation analysis showed that the levels of serum miR-212-5p and miR-221-3p of patients with AECOPD were negatively correlated with the levels of TLR4 mRNA and NF-κB mRNA(P<0.05).The levels of serum interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in the good prognosis group were lower than those in the poor prognosis group,and the differences were statistically significant(P<0.05).Multivariate Logistic regression analysis results showed that the elevated levels of IL-6,TNF-α,TLR4 mRNA and NF-κB mRNA were the risk factors for the poor prognosis of patients with AECOPD(P<0.05),and elevated levels of miR-212-5p and miR-221-3p were the protective factors for the poor prognosis of patients with AECOPD(P<0.05).The results of ROC curve showed that the area under the curve(AUC)of serum miR-212-5p and miR-221-3p in combination for predicting poor prognosis of AECOPD was 0.862,which was significantly higher than miR-212-5p(0.722)and miR-221-3p(0.755)alone(P<0.05).Conclusion Down-regulation of serum miR-212-5p and miR-221-3p levels can lead to poor prognosis of patients with AECOPD,which may be related to regulate the TLR4/NF-κB inflammatory signaling pathway,and the combined detection of the above two indicators has high predictive value for the prognosis of patients with AECOPD.