老年COPD合并Ⅱ型呼吸衰竭患者外周血氧化应激信号传导通路关键mRNA的表达意义-东南大学学报医学版

老年COPD合并Ⅱ型呼吸衰竭患者外周血氧化应激信号传导通路关键mRNA的表达意义

单位：1. 达州市中西医结合医院, 四川达州 635000;
2. 达州市中心医院, 四川达州 635000

分类号：R563

出版年·卷·期（页码）：2023·42·第四期（519-525）

摘要：

目的:探究老年慢性阻塞性肺疾病(COPD)合并Ⅱ型呼吸衰竭患者外周血氧化应激信号传导通路关键mRNA的表达意义。方法:选取2020年7月至2022年6月达州市中西医结合医院60例老年COPD合并Ⅱ型呼吸衰竭患者作为观察组,另选取同期收治60例老年COPD患者不合并呼吸衰竭作为对照组。比较两组外周血Keap1、核因子E2相关因子2(Nrf2)、抗氧化反应元件(ARE)mRNA表达,分析外周血Keap1、Nrf2、ARE mRNA与老年COPD合并Ⅱ型呼吸衰竭的关系,比较死亡与生存患者外周血Keap1、Nrf2、ARE mRNA表达与肺功能指标的相关性,评价外周血Keap1、Nrf2、ARE mRNA对老年COPD合并Ⅱ型呼吸衰竭患者死亡风险的预测价值。结果:观察组外周血Keap1 mRNA表达较对照组高,Nrf2及ARE mRNA较对照组低(P＜0.05);Keap1、Nrf2及ARE mRNA与老年COPD患者合并Ⅱ型呼吸衰竭独立相关,Keap1 mRNA表达越高,Nrf2及ARE mRNA表达越低,老年COPD患者合并Ⅱ型呼吸衰竭风险越大(P＜0.05)。60例老年COPD合并Ⅱ型呼吸衰竭患者住院28 d病死16例,生存44例。死亡患者外周血Keap1 mRNA表达较生存患者高,Nrf2及ARE mRNA、FEV1、FVC、FEV1占预计值百分比较生存患者低(P＜0.05);老年COPD合并Ⅱ型呼吸衰竭患者外周血Keap1、Nrf2及ARE mRNA表达与FEV1呈负相关关系,与FVC、FEV1占预计值百分比呈正相关关系(P＜0.05);Keap1、Nrf2及ARE mRNA预测老年COPD合并Ⅱ型呼吸衰竭患者死亡的AUC分别为0.778(95%CI:0.652~0.875)、0.706(95%CI:0.574~0.817)、0.765(95%CI:0.627~0.857),联合预测AUC为0.920(95%CI:0.821~0.975);进一步对各预测方案预测价值比较显示,Keap1、Nrf2及ARE mRNA联合预测的AUC明显较单一指标高(均P＜0.05)。根据ROC曲线中Keap1、Nrf2及ARE mRNA截断值,将其分为高表达亚组(＞截断值)与低表达亚组(≤截断值),老年COPD合并Ⅱ型呼吸衰竭患者外周血Keap1、Nrf2及ARE mRNA不同表达时死亡风险相差5.133、0.273、4.500倍。结论:老年COPD合并呼吸衰竭患者Keap1-Nrf2/ARE信号传导通路中Keap1 mRNA表达上调,Nrf2及ARE mRNA表达下降,且与患者肺功能及死亡风险密切相关。

Objective: To investigate the significance of mRNA expression in the peripheral blood oxidative stress signaling pathway in elderly patients with chronic obstructive pulmonary disease(COPD) combined with type Ⅱ respiratory failure. Methods: 60 elderly COPD patients with combined type Ⅱ respiratory failure in our hospital from July 2020 to June 2022 were selected as the observation group, and another 60 elderly COPD patients without combined respiratory failure admitted in the same period were selected into control group. We compared the mRNA expression of peripheral blood Keap1, nuclear factor E2-related factor 2(Nrf2) and antioxidant response element(ARE) between the two groups and analyzed the relationship between peripheral blood Keap1, Nrf2 and ARE mRNA and elderly COPD combined with type Ⅱ respiratory failure, we also compared the mRNA expression of peripheral blood Keap1, Nrf2 and ARE with lung function indexes in death or survial patients, and evaluated the correlation between peripheral blood Keap1, Nrf2 and ARE mRNA expression and lung function indexes. The predictive value of peripheral blood Keap1, Nrf2 and ARE mRNA on the risk of death in elderly patients with COPD combined with type Ⅱ respiratory failur was evaluated. Results: In the observation group, the expression of Keap1 mRNA in peripheral blood was higher than that in the control group, and the expressions of Nrf2 and ARE mRNA were lower than that in the control group(P<0.05); Keap1, Nrf2 and ARE mRNA were independently associated with combined type Ⅱ respiratory failure in elderly COPD patients, the higher the expression of Keap1 mRNA, the lower the expressions of Nrf2 and ARE mRNA, the higher the risk of combined type Ⅱ respiratory failure in elderly COPD patients(P<0.05). The higher the expression of Keap1 mRNA, the lower the expressions of Nrf2 and ARE mRNA, the greater the risk of type Ⅱ respiratory failure in elderly COPD patients(P<0.05); Among 60 elderly COPD patients with type Ⅱ respiratory failure, 16 cases died after 28 days of hospitalization while 44 survived. The expression of Keap1 mRNA in peripheral blood was higher in patients who died than in those who survived, and the percentages of Nrf2 and ARE mRNA, FEV1, FVC and FEV1 in the expected value were lower than those in the survived(P<0.05); the expression of Keap1, Nrf2 and ARE mRNA in peripheral blood were negatively correlated with FEV1 in elderly patients with COPD combined with type Ⅱ respiratory failure, while there were positive correlation with the FVC and the percentage of FEV1 in the expected value. The AUCs for Keap1, Nrf2 and ARE mRNA to predict the prognosis of elderly patients with COPD combined with type Ⅱ respiratory failure were 0.778(95%CI:0.652-0.875), 0.706(95%CI:0.574-0.817), 0.765(95%CI:0.627-0.857), and the combined predicted AUC was 0.920(95%CI:0.821-0.975)(all P<0.001).Further comparison of the predictive value of each prediction scheme showed that the AUC predicted by the combination of Keap1, Nrf2 and ARE mRNA was significantly higher than that of the single index(all P<0.05); according to the cut-off values of Keap1, Nrf2 and ARE mRNA in the ROC curve, they were divided into high expression subgroup(> cut-off value) and low expression subgroup(≤cut-off value), and the risk of death of elderly COPD patients combined with severe respiratory failure was 5.133-fold, 0.273-fold and 4.500-fold between high expression subgroup and low expression subgroud. Conclusion: Keap1 mRNA expression is upregulated in the Keap1-Nrf2/ARE signaling pathway, and Nrf2 and ARE mRNA expressions are decreased in elderly patients with COPD combined with respiratory failure, which is closely associated with the patients' lung function and mortality risk.

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