COPD rat model is more susceptible to cold stress and PM2.5 exposure and the underlying mechanism

et al. 2020

Environ Health

Background: Exposure to air pollution is associated with chronic obstructive pulmonary disease (COPD). However, findings on the effects of air pollution on lung function and systemic inflammation in Chinese COPD patients are inconsistent and scarce. This study aims to evaluate the effects of ambient air pollution on lung function parameters and serum cytokine levels in a COPD cohort in Beijing, China. Methods: We enrolled COPD participants on a rolling basis from December 2015 to September 2017 in Beijing, China. Follow-ups were performed every 3 months for each participant. Serum levels of 20 cytokines were detected every 6 months. Hourly ambient pollutant levels over the same periods were obtained from 35 monitoring stations across Beijing. Geocoded residential addresses of the participants were used to estimate daily mean pollution exposures. A linear mixed-effect model was applied to explore the effects of air pollutants on health in the first-year of follow-up. Results: A total of 84 COPD patients were enrolled at baseline. Of those, 75 COPD patients completed the first-year of follow-up. We found adverse cumulative effects of particulate matter less than 2.5 μm in aerodynamic diameter (PM 2.5), nitrogen dioxide (NO 2), sulfur dioxide (SO 2) and carbon monoxide (CO) on the forced vital capacity % predicted (FVC % pred) in patients with COPD. Further analyses illustrated that among COPD patients, air pollution exposure was associated with reduced levels of serum eotaxin, interleukin 4 (IL-4) and IL-13 and was correlated with increased serum IL-2, IL-12, IL-17A, interferon γ (IFNγ), monocyte displacing protein 1 (MCP-1) and soluble CD40 ligand (sCD40L). Conclusion: Acute exposures to PM 2.5 , NO 2 , SO 2 and CO were associated with a reduction in FVC % pred in COPD patients. Furthermore, short-term exposure to air pollutants increased systemic inflammation in COPD patients; this may be attributed to increased Th1 and Th17 cytokines and decreased Th2 cytokines.

Section: Discussionsupporting

confidence: 51%

Lung function and systemic inflammation associated with short-term air pollution exposure in chronic obstructive pulmonary disease patients in Beijing, China

et al. 2020

Environ Health

“…Research found that COPD rats may be more susceptible to cold stress. Cold stress may aggravate PM2.5-induced toxic effects in the lung of COPD rats through increasing Ang-II/NF- κ B signaling pathway and suppressing Nrf2 signaling pathway [26]. Cold and dry air contributed to the excessive productions of mucus and drying of mucus in airway, which led to the impaired mucociliary clearance of airway surface, a critical innate defense mechanism in upper airway, and ultimately the occurrence of airway obstruction [27–29].…”

Section: Discussionmentioning

confidence: 99%

Effects of Modified Zhisou Powder on Airway Mucus Production in Chronic Obstructive Pulmonary Disease Model Rats with Cold‐Dryness Syndrome

Evidence-Based Complementary and Alternative Medicine

Wang

Jing

et al. 2018

Objective. In China, the Chinese medicine formula modified zhisou powder (MZP) is commonly used to treat COPD with cold-dryness syndrome (CDSCOPD) to relieve cough and sputum. However, the underlying mechanisms of MZP on treating CDSCOPD remain to be elucidated. Methods. COPD and CDSCOPD rat models were established; MZP was given to CDSCOPD rats in the last 7 days of the 97-day model establishment. Then the rats were subjected to lung function measurement. Pathological changes in lungs were observed through paraffin section and H&E staining. The mRNA and protein levels of AQP1, 4, and 5 and Muc5AC and Muc5B in lung were determined by quantitative RT-PCR and western blotting. NE levels was determined by ELISA. Results. The impaired lung functions were observed in rats exposed to cigarette smoke. Among all parameters evaluating lung functions, only tidal volume demonstrates a further decrease in CDSCOPD when compared with COPD, indicating further impaired pulmonary ventilation functions upon cold-dryness stimulation. The intervention of MZP effectively improved lung functions parameters, prevented the inflammations, and eliminated the increases of AQP4 and 5 and the decrease of Muc5AC in lung. Conclusion. MZP probably improves pulmonary functions in CDSCOPD through inhibiting lung inflammation, increasing expressions of AQPs, and decreasing Muc5AC expression in lung.

“…Therefore, it is well-accepted that dysregulation of circulatory/systemic or local/tissue ACE/ Ang II/AT1R axis components can lead to vascular tissue related damages, including effects on vascular tone and proliferation of vascular smooth muscle cells (Daemen et al, 1991;Te Riet et al, 2015;Xu et al, 2017a). Recent reports have provided evidences that PM 2.5 exposure altered the Ang II and ACE expression (Wang et al, 2016;Zhang et al, 2018). Delfino et alreported that the expression levels of AGT, ACE and AT1R were significantly increased in endothelial cells of the rat aorta following PM 2.5 exposure (Delfino et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

The Role of Nrf2 in the PM-Induced Vascular Injury Under Real Ambient Particulate Matter Exposure in C57/B6 Mice

Luo

et al. 2021

Front. Pharmacol.

Short-and long-term exposure to particulate matter (PM) has been associated with cardiovascular disease (CVD). It is well recognized that oxidative stress is a potential major mechanism in PM-induced vascular injuries, in which the nuclear factor E2-related factor 2 (Nrf2) signaling pathway plays a critical role. In the current study, a Nrf2 knockout mouse model was used in combination with an individual ventilated cage (IVC)-based real-ambient PM exposure system to assess the potential vascular injury and the potential role of Nrf2 in the angiotensin II (Ang II)-associated vascular injury. After 6-or 11-week exposure to PM, the histopathology assay revealed that PM exposure resulted in the thickening of the walls of vascular. After 6 weeks exposure to PM, the ELISA assay revealed that PM exposure resulted in the elevated plasma concentration of Ang II. The expression levels of genes of interest were then further investigated with quantitative real-time PCR. Notably, the results showed that Angiotensinogen (AGT), Angiotensin converting enzyme (ACE) and Angiotensin type I receptor (AT1R) were involved in PM-induced pathological changes. Western blotting for ACE showed similar results. Moreover, the extent of vascular thickening and the Ang II elevation was most prominent in the Nrf2 gene knockout PM exposure group (KOE). Furthermore, the expression of Nrf2 downstream relevant genes (HO1, Nqo1, Gclc, Gsta4) were significantly enhanced in the wildtype PM exposure group (WTE), while those were remarkably suppressed in the Nrf2 gene knockout groups. The ELISA result of monocyte chemoattractant protein-1 (MCP-1) serum levels in the KOE group was significantly higher in relation to that in the Nrf2 knockout control group (KOC). In summary, PM exposure is associated with thickening of vascular wall, while Nrf2 knockout may further enhance this effect. A potential mechanistic contributor of such effects is the activation of ACE/ANGII/AT1R axis, in which Nrf2 played a regulatory role.