Keap1-Nrf2-ARE通路对老年COPD合并重症呼吸衰竭患者病死风险的预测价值

Predictive Value of Keap1-Nrf2-ARE Pathway for the Risk of Death of Elderly Patients with COPD Complicated with Severe Respiratory Failure

目的探讨Keap1-Nrf2-ARE通路对老年慢性阻塞性肺疾病(COPD)合并重症呼吸衰竭患者死亡风险的预测价值。方法选取河南科技大学附属许昌市中心医院2020年1月至2022年6月收治的124例老年COPD合并重症呼吸衰竭患者为研究组,选取同期124例老年COPD未合并重症呼吸衰竭患者为对照组,根据治疗28 d的预后情况将研究组分为病死(42例)和生存(82例)2个亚组。比较两组入院时、不同预后患者入院时、治疗7 d、14 d后外周血Kelch样环氧氯丙烷相关蛋白-1(Keap1)、核因子E2(Nrf2)、抗氧化反应原件(ARE)表达水平及急性生理学与慢性健康状况Ⅱ(APACHEⅡ)评分,分析入院时外周血Keap1、Nrf2、ARE表达水平与APACHEⅡ评分及合并重症呼吸衰竭的相关性,偏回归分析老年COPD合并重症呼吸衰竭患者病死的影响因素,采用受试者工作特征(ROC)曲线分析外周血Keap1、Nrf2、ARE表达水平对老年COPD合并重症呼吸衰竭患者病死的预测价值。结果研究组入院时外周血Keap1、Nrf2、ARE表达水平低于对照组,APACHEⅡ评分高于对照组(P<0.05);入院时外周血Keap1、Nrf2、ARE表达水平与APACHEⅡ评分及合并重症呼吸衰竭均呈负相关(P<0.05)。治疗7、14 d后病死患者外周血Keap1、Nrf2、ARE表达水平低于生存患者(P<0.05)。logistic回归分析结果显示,治疗7、14 d后外周血Keap1、Nrf2、ARE表达水平为老年COPD合并重症呼吸衰竭患者病死的保护因素(P<0.05)。ROC分析结果显示,治疗7、14 d后外周血Keap1、Nrf2、ARE表达水平联合预测老年COPD合并重症呼吸衰竭患者病死的曲线下面积(AUC)分别为0.740、0.818,均高于单一指标预测(P<0.05)。结论Keap1、Nrf2、ARE参与老年COPD合并重症呼吸衰竭发生发展,且在辅助临床预测病死风险方面具有较高效能。

Objective To investigate the predictive value of Keap1-Nrf2-ARE pathway for the risk of death in elderly patients with chronic obstructive pulmonary disease(COPD)combined with severe respiratory failure.Methods A total of 124 elderly patients with COPD combined with severe respiratory failure admitted to Xuchang Central Hospital Affiliated to Henan University of Science and Technology from January 2020 to June 2022 were selected as the study group,and 124 elderly patients with COPD without severe respiratory failure during the same period were selected as the control group.According to the prognosis after 28 days of treatment,the study group were divided into two subgroups,death(42 cases)and survival(82 cases).The expression levels of Kelch-like epichlorohydrin-associated protein-1(Keap1),nuclear factor E2(Nrf2)and antioxidant response element(ARE)in peripheral blood and acute physiology and chronic health statusⅡ(APACHEⅡ)scores were compared between the two groups on admission and patients with different prognosis,7 and 14 days after treatment were comoard.The correlation between the expression levels of Keap1,Nrf2 and ARE in peripheral blood on admission and APACHEⅡscore and severe respiratory failure were analyzed,and partial regression was used to analyze the influencing factors of death in elderly patients with COPD combined with severe respiratory failure.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of peripheral blood Keap1,Nrf2,ARE expression levels for mortality in elderly COPD patients with severe respiratory failure.Results The expression levels of Keap1,Nrf2 and ARE in the peripheral blood of the study group were lower than those of the control group,and the APACHEⅡscore was higher than that of the control group(P<0.05).The expression levels of Keap1,Nrf2 and ARE in peripheral blood were negatively correlated with APACHEⅡscore and severe respiratory failure(P<0.05).The expression levels of Keap1,Nrf2 and ARE in peripheral blood of patients who died after 7 and 14 days of treatment were lower than those of patients who survived(P<0.05).Logistic regression analysis showed that Keap1,Nrf2,ARE levels after 7 and 14 days of treatment were protective factors for death in elderly patients with COPD combined with severe respiratory failure(P<0.05).After 7 and 14 days of treatment,the combined prediction of Keap1,Nrf2,and ARE expression levels in peripheral blood for mortality in elderly COPD patients with severe respiratory failure had area under the curve(AUC)values of 0.740 and 0.818,respectively,which were higher than those predicted by a single indicator(P<0.05).Conclusion Keap1,Nrf2 and ARE are involved in the occurrence and development of COPD complicated with severe respiratory failure in the elderly,and have high efficacy in assisting clinical prediction of the risk of death.