ZFP36/ZFP36L1在慢性阻塞性肺疾病患者外周血中的表达及意义
Expression and significance of ZFP36/ZFP36L1 in peripheral blood of Patients with chronic obstructive pulmonary disease
陈致润 1陈林 1何振华 1刘莎 1文星雅 1肖玉蓉1
作者信息
- 1. 南华大学衡阳医学院,附属第二医院呼吸与危重症医学科(湖南衡阳 421001)
- 折叠
摘要
目的 探究锌指蛋白 36(zinc finger protein 36,ZFP36)和锌指蛋白 36L1(zinc finger protein 36L1,ZFP36L1)在慢性阻塞性肺疾病(简称慢阻肺)患者外周血中的表达及意义.方法 纳入42例慢阻肺急性加重期、21例慢阻肺稳定期和18例健康人,收集外周血标本后分别ELISA、qPCR法检测ZFP36、ZFP36L1蛋白和mRNA表达水平.比较三组研究对象ZFP36、ZFP36L1表达水平差异.采用Spearman法分析相关因素,采用受试操作特征(receiver operating characteristic,ROC)曲线分析ZFP36、ZFP36L1对慢阻肺稳定期和慢阻肺急性加重的诊断及对近期频繁加重的预测价值.结果 与健康组比较,慢阻肺稳定组ZFP36L1蛋白表达下调;与慢阻肺稳定组相比,慢阻肺急性加重组ZFP36蛋白表达下调.蛋白表达结果与血清中ZFP36、ZFP36L1 mRNA表达水平差异相同.ZFP36和ZFP36L1与炎症指标呈负相关,ZFP36水平与ZFP36L1、肺功能呈正相关,与吸烟指数、改良英国医学研究委员会呼吸困难问卷评分、住院期间发生呼吸衰竭、3个月内再加重次数、总住院次数呈负相关.ZFP36诊断慢阻肺急性加重的曲线下面积(area under the curve,AUC)为0.980,敏感性为95.2％,特异性为90.5％,联合第1秒用力呼气容积占预计值百分比诊断慢阻肺急性加重的AUC为0.985,敏感性为92.9％,特异性为100％.联合中性粒细胞淋巴细胞比值(neutrophil to lymphocyte ratio,NLR)预测慢阻肺急性加重患者出院后近期再加重的敏感性66.7％,特异性88.9％.ZFP36、ZFP36L1和IL-8辅助诊断慢阻肺的AUC分别为0.889、0.989、0.981,敏感性为61.9％、90.5％、95.2％,特异性为100％、100％、94.4％.结论 外周血中ZFP36对慢阻肺急性加重具有良好的诊断价值.联合第1秒用力呼气容积占预计值百分比可进一步增加诊断价值.作为慢阻肺患者出院3个月内频繁加重的预测指标,预测敏感性、特异性优于中性粒细胞淋巴细胞比值等炎症指标.ZFP36在慢阻肺急性加重中具有抗炎作用.外周血中ZFP36L1具有良好的诊断慢阻肺的价值.
Abstract
Objective Investigate zinc finger protein 36(ZFP36)and zinc finger protein 36L1(ZFP36L1)expression in peripheral blood of patients with chronic obstructive pulmonary disease(COPD).Methods Peripheral blood samples were collected from 42 individuals with acute exacerbation of COPD(AECOPD),21 with stable COPD,and 18 healthy participants.The levels of ZFP36 and ZFP36L1 proteins and mRNA expressions were evaluated using ELISA and qPCR techniques.Difference in expression levels among the three groups was examined.Spearman analysis and receiver operating characteristic(ROC)curve were carried out for assessment of diagnostic and predictive value of FP36 and ZFP36L1 for COPD and AECOPD.Results Compared with the healthy group,ZFP36L1 protein expression was downregulated in the COPD stable group.ZFP36 protein expression was downregulated in the AECOPD group compared with the COPD stable group.Similar differences were observed in mRNA expression levels.ZFP36 and ZFP36L1 levels were negatively correlated with inflammatory markers.ZFP36 levels were positively correlated with ZFP36L1 and lung function,and negatively correlated with smoking index,modified Medical Research Council score,occurrence of respiratory failure during hospitalization,exacerbation frequency within 3 months,and total hospitalizations.The area under the curve(AUC)for diagnosing AECOPD using ZFP36 was 0.980,with sensitivity of 95.2％and specificity of 90.5％.When combined with FEV1％pred,the AUC improved to 0.985,with sensitivity of 92.9％and specificity of 100％.For predicting post-discharge exacerbations in AECOPD when combined with neutrophil-to-lymphocyte ratio(NLR),sensitivity of ZFP36 alone was 66.7％and specificity was 88.9％.The AUCs for diagnosing COPD using ZFP36,ZFP36L1,and interleukin-8(IL-8)were 0.889,0.989,and 0.981,respectively.The sensitivities were 61.9％,90.5％,and 95.2％,and specificities were 100％,100％,and 94.4％,respectively.Conclusions Peripheral blood ZFP36 has good diagnostic value for AECOPD.Combined with FEV1％pred,it can further increase diagnostic value.As a predictive indicator for frequent exacerbations within 3 months of discharge in COPD patients,its predictive sensitivity and specificity are superior to inflammatory markers such as NLR.ZFP36 exhibits anti-inflammatory effects in AECOPD.Peripheral blood ZFP36L1 has good diagnostic value for COPD.
关键词
慢性阻塞性肺疾病/锌指蛋白36/锌指蛋白36L1/白细胞介素8/诊断Key words
Chronic obstructive pulmonary disease/zinc finger protein 36/zinc finger protein 36L1/interleukin-8/diagnosis引用本文复制引用
基金项目
湖南省自然科学基金(2023JJ60352)
出版年
2024
NETL
NSTL
万方数据