Smoking cessation regulates PI3K-Akt-FoxO1 signaling pathway in patients with chronic obstructive pulmonary disease
10.3760/cma.j.cn341190-20240427-00474
- VernacularTitle:戒烟对COPD患者PI3K-Akt-FoxO1信号通路的调控作用
- Author:
Ying ZHONG
1
;
Youyi DU
1
;
Yiru YE
1
;
Xuefang XIONG
1
Author Information
1. 丽水市中心医院呼吸与危重症医学科，丽水 323000
- Publication Type:Journal Article
- Keywords:
Pulmonary disease,chronic obstructive;
Smoking;
Smoking cessation;
Respiratory function tests;
Phosphatidylinositol 3-kinases;
Transcriptional activation;
A
- From:
Chinese Journal of Primary Medicine and Pharmacy
2025;32(7):968-974
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effects of smoking cessation on lung function improvement in patients with chronic obstructive pulmonary disease (COPD) and the related mechanisms.Methods:A case-control study was conducted involving 184 patients with COPD admitted to the Department of Respiratory and Critical Care Medicine at Lishui Central Hospital from January 2022 to May 2023. Based on smoking behavior following 6-month smoking cessation intervention, the patients were categorized into three groups: 56 patients who continued to smoke (control group), 63 patients who completely quit smoking (observation group), and the remaining 65 patients who were partial quitters. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV 1), and peak expiratory flow rate were monitored before and after the intervention in both the control and observation groups. Additionally, serum levels of interleukin-6 (IL-6), interleukin-1 beta (IL-1β), tumor necrosis factor alpha, nuclear factor kappa B (NF-κB), malondialdehyde, superoxide dismutase, and glutathione peroxidase were measured. Western blotting was performed to detect the protein levels of phosphoinositide 3-kinase (PI3K), serine/threonine kinase (Akt), Forkhead box protein O1 (FoxO1), IL-6, IL-1β, NF-κB, nuclear factor erythroid 2-related factor 2, and heme oxygenase-1 in peripheral blood cells. FoxO1 chromatin immunoprecipitation sequencing was performed to analyze FoxO1-bound chromatin. Results:After smoking cessation intervention, the FEV 1, FVC, FEV 1/FVC ratio, and peak expiratory flow rate in the observation group were (1.29 ± 0.32) L, (1.96 ± 0.36) L, (71.81 ± 8.57)%, and (2.58 ± 0.72) L/s, respectively, which were significantly higher than those in the control group [(1.10 ± 0.37) L, (1.72 ± 0.34) L, (63.17 ± 8.82)%, (2.20 ± 0.71) L/s, t = -3.00, -3.73, -5.42, -2.89, all P < 0.01]. The serum levels of IL-6, NF-κB, IL-1β, and tumor necrosis factor alpha in the observation group were (21.67 ± 3.25) ng/L, (19.58 ± 4.02) ng/L, (24.30 ± 4.03) ng/L, and (270.14 ± 32.49) ng/L, respectively, which were significantly lower than those in the control group [(39.18 ± 4.34) ng/L, (35.48 ± 4.17) ng/L, (34.42 ± 4.05) ng/L, (445.04 ± 39.12) ng/L, t = 25.08, 21.16, 13.64, 26.63, all P < 0.001]. Additionally, the serum malondialdehyde level in the observation group was significantly lower than that in the control group ( t = 29.08, P < 0.001). In contrast, the levels of superoxide dismutase and glutathione peroxidase in the observation group were significantly higher than those in the control group ( t = -9.21, -9.59, both P < 0.001). The phosphorylation levels of PI3K, Akt, and FoxO1 in peripheral blood cells were significantly lower in the observation group compared with the control group ( t = 6.64, 9.35, 7.12, all P < 0.001). FoxO1 bound to genes involved in inflammation and oxidative stress signaling pathways. The levels of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 in the observation group were significantly higher than those in the control group ( t = -4.97, -10.49, both P < 0.05). Conclusions:Smoking cessation intervention can inhibit PI3K/Akt phosphorylation in patients with COPD, and then activate FoxO1, exert anti-inflammatory and antioxidant effects, and inhibit the deterioration of lung function in patients with COPD who smoke.
