高强度间歇运动通过miR-124-3p/ERN1轴抑制吸烟相关的老年慢性阻塞性肺疾病炎症反应的机制

The mechanism of high-intensity intermittent exercise inhibiting the inflammatory response of elderly patients with smoking-re-lated chronic obstructive pulmonary disease through the miR-124-3p/ERN1 Axis

中文关键词: 老年  慢性阻塞性肺疾病  微小RNA-124-3p  内质网到核信号1  肺康复  炎症

英文关键词: elderly  chronic obstructive pulmonary disease  miR-124-3p  endoplasmic reticulum to nuclear signaling 1  pulmonary rehabilitation  inflammation

中文摘要:

      目的 探讨miR-124-3p/ERN1 轴在运动改善慢性阻塞性肺疾病(COPD)患者机体炎症反应中的作用机制.方法 选择2020 年11 月15 日—2021 年11 月30 日于浦东新区公利医院呼吸科诊治的150 例患者作为研究对象,分为非吸烟组(非吸烟且肺功能正常者,n =50)和吸烟非COPD组(吸烟且肺功能正常者,n =50)、COPD组(COPD患者,n = 50).COPD患者接受运动训练前后,检测并比较3 组外周血清miR-124-3p、ERN1 表达差异;用香烟烟雾提取物处理支气管上皮细胞建立细胞模型,检测miR-124-3p、ERN1 及炎症因子的表达水平;采用CCK-8 法和流式细胞术检测细胞活力和凋亡;利用生物信息学分析、荧光素酶报告分析和RT-qPCR检测并阐明miRNA和mRNA之间的相互关系.结果 COPD患者血清中miR-124-3p表达水平低于吸烟者及非吸烟者,ERN1 表达水平高于吸烟者及非吸烟者,运动训练后则可逆转以上因子的表达水平,差异均有统计学意义(P＜0.001、P＜0.05);上调miR-124-3p可抑制其下游靶标ERN1 的表达,降低CSE刺激下支气管上皮细胞炎症因子水平.结论 运动训练可增加COPD患者血清miR-124-3p表达水平,其机制可能与通过靶向ERN1 途径减轻与吸烟相关的COPD炎症反应有关.

英文摘要:

      Objective To explore the mechanism of action of miR?124?3p / ERN1 axis in improving the inflammatory response of patients with chronic obstructive pulmonary disease (COPD) through exercise. Methods 150 patients diagnosed and treated in Respiratory Department of Gongli Hospital in Pudong New District from November 15, 2020 to November 30, 2021 were selected as the research subjects. They were divided into non?smoking group (non?smoking with normal lung func? tion, n =50), smoking non?COPD group (smoking with normal lung function, n = 50) and COPD group (COPD patients, n =50). Before and after receiving exercise training for COPD patients, the expression differences of miR?124?3p and ERN1 in the peripheral serum of three groups were detected and compared. A cell model of bronchial epithelial cells exposed to cigarette smoke extract (CSE) was established, and the expression levels of miR?124?3p, ERN1 and inflammatory factors were detec? ted. CCK?8 assay and flow cytometry were used to detect cell viability and apoptosis. The bioinformatics analysis, luciferase report analysis and RT?qPCR were used to detect and elucidate the relationship between miRNA and mRNA. Results The ex? pression level of miR?124?3p in serum of COPD patients was lower than that of the smokers and non?smokers, while the expres? sion level of ERN1 was higher than that of the smokers and non?smokers. The expression levels of the above factors could be reversed after exercise training, and the differences were statistically significant (P <0. 001, P <0. 05). Upregulation of miR? 124?3p could inhibit the expression of its downstream target ERN1 and reduce the level of inflammatory factors in bronchial epi? thelial cells stimulated by CSE. Conclusion Exercise training can increase the expression level of serum miR?124?3p in COPDpatients, and its mechanism may be related to the reduction of smoking?related COPD inflammatory response through targeted ERN1 pathway.