稳定期COPD患者下呼吸道细菌定植对血清TIMP-1及NF-κB mRNA与β-catenin mRNA表达水平的影响

Effect of bacterial colonization in lower respiratory tract on expression levels of serum TIMP-1,NF-κB mRNA and β-catenin mRNA in patients with stable COPD

目的 分析稳定期慢性阻塞性肺疾病(COPD)患者下呼吸道细菌定植对血清基质金属蛋白酶抑制剂-1(TIMP-1)及核因子-κB(NF-κB)信使核糖核苷酸(mRNA)、β-连环蛋白(β-catenin)mRNA表达水平的影响。方法 2020年4月-2022年12月山东第一医科大学附属济南人民医院收治的110例稳定期COPD患者纳入研究。其中44例稳定期COPD患者发生下呼吸道细菌定植纳入研究组,66例未发生下呼吸道细菌定植纳入对照组。分析病原菌分布情况,两组及不同COPD病情分级患者血清TIMP-1及NF-κB mRNA、β-catenin mRNA表达水平,绘制受试者工作特征(ROC)曲线分析血清TIMP-1及NF-κB mRNA、β-catenin mRNA表达水平单独及联合检测对稳定期COPD患者下呼吸道细菌定植的诊断价值。结果 110例稳定期COPD患者发生下呼吸道细菌定植44例,发生率为40.00%,共分离病原菌49株,其中革兰阴性菌33株(67.35%);与对照组比较,研究组血清TIMP-1及NF-κB mRNA、β-catenin mRNA表达水平更高(P<0.05);COPDⅠ组、COPDⅡ组、COPDⅢ组血清TIMP-1及NF-κB mRNA、β-catenin mRNA表达水平呈升高趋势(P<0.05);绘制ROC曲线分析血清TIMP-1及NF-κB mRNA、β-catenin mRNA表达水平联合检测对稳定期COPD患者下呼吸道细菌定植的曲线下面积(AUC)、敏感性、特异性均最高。结论 稳定期COPD患者下呼吸道细菌定植主要病原菌为革兰阴性菌,随着下呼吸道细菌定植的发生、COPD病情分级恶化血清TIMP-1及NF-κB mRNA、β-catenin mRNA表达水平升高,且各项指标联合检测对稳定期COPD患者下呼吸道细菌定植的预测价值更高。

OBJECTIVE To analyze the effect of bacterial colonization in lower respiratory tract on the expression levels of tissue inhibitor of metalloproteinase 1(TIMP-1), nuclear factor-κB(NF-κB) messenger ribonucleotide(mRNA) and β-catenin mRNA in patients with stable chronic obstructive pulmonary disease(COPD). METHODS A total of 110 patients with stable COPD admitted to Jinan People′s Hospital Affiliated to Shandong First Medical University from Apr 2020 to Dec 2022 were included in the study. Forty-four patients with stable COPD complicated with lower respiratory tract bacterial colonization were included in the study group, and 66 cases without lower respiratory tract bacterial colonization were included in the control group. Pathogenic bacteria distribution, expression levels of serum TIMP-1, NF-κB mRNA and β-catenin mRNA in different COPD disease grades of the two groups were analyzed. Receiver operating characteristic(ROC) curve was drawn to analyze the diagnostic value of expression levels of serum TIMP-1, NF-κB mRNA and β-catenin mRNA in patients with stable COPD for bacterial colonization in lower respiratory tract. RESULTS Bacterial colonization of lower respiratory tract occurred in forty-four cases of 110 patients with stable COPD, with an incidence of 40.00%. A total of 49 strains of pathogenic bacteria were isolated, including 33 gram-negative bacteria(67.35%). Compared with the control group, the expression level of serum TIMP-1 and mRNA levels of NF-κB and β-catenin in the study group were higher(P<0.05). The expression levels of serum TIMP-1, NF-κB mRNA and β-catenin mRNA in the COPD Ⅰ, COPD Ⅱ and COPD Ⅲ groups showed an increased tend(P<0.05). The lower respiratory tract bacterial colonization in patients with stable COPD was positive, while negative in patients without lower respiratory tract bacterial colonization. ROC curve analysis showed the area under the curve(AUC), sensitivities and specificities of the combined detection of bacterial colonization in lower respiratory tract of patients with stable COPD were the highest. CONCLUSION The main pathogen of bacterial colonization in lower respiratory tract of patients with stable COPD was gram-negative bacteria. With the occurrence of bacterial colonization of lower respiratory tract and the deterioration of COPD disease grade increase, the expression levels of serum TIMP-1, NF-κB mRNA and β-catenin mRNA are upregulated. Moreover, combined detection had higher predictive value in bacterial colonization in lower respiratory tract of patients with stable COPD.