• Department of Geriatric Respiratory Medicine, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P. R. China;
LIU Xiaoju, Email: liuxiaoju835@126.com
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Objective  To observe the effects of fine particulate matter (PM2.5) on airway remodeling and Notch signaling pathway in mice with bronchial asthma, and explore the possible mechanism of its influence on airway remodeling in asthmatic mice. Methods  Forty eight-week-old SPF female BALB/c mice were divided into a healthy control group, a healthy PM2.5 group, an asthma group and an asthma PM2.5 group by random number table, with 10 mice in each group. The asthma group and the asthma PM2.5 group were sensitized with ovalbumin to establish asthma mouse model, and the healthy PM2.5 group and the asthma PM2.5 group received aerosol inhalation of PM2.5 (510 μg/m3) after each provocation. After modeling, lung function was measured in each group. Hematoxylin and eosin staining and Masson staining were performed on the lung tissue sections of mice. Image analysis software was used to determine the circumference of the bronchial basement membrane, the total area of the bronchial wall, the area of bronchial smooth muscle and the area of collagen deposition. The expressions of Notch1, Hes1, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1) and type Ⅰ collagen (Col-Ⅰ) were detected by immunohistochemistry and western blotting. The content of hydroxyproline (HYP) in lung tissue was determined by alkaline water method. Results  The total airway wall area, airway smooth muscle area and collagen deposition area in the asthma group [(365.81±46.10), (132.80±20.14), (221.82±25.20) μm2/μm] were significantly higher than those in the healthy control group [(187.70±14.80), (89.73±8.49), (123.91±16.88) μm2/μm] (P<0.01). The healthy PM2.5 group [(244.62±42.86), (116.40±20.40), (174.91±57.41) μm2/μm] and the asthma PM2.5 group [(447.70±76.14), (236.14±36.35), (294.89±75.96) μm2/μm] were higher than those in the control group (all P<0.01). The expressions of Notch1, Hes1, α-SMA, TGF-β1 and Col-Ⅰ were strongly positive in the lung tissues of the asthmatic mice, but weak in the healthy control group. After PM2.5 intervention, compared with the control group, the expression intensity of the above molecules increased. Notch1 receptor and downstream Hes1 protein in the asthma group (0.86±0.10, 1.02±0.06) were significantly higher than those in the healthy control group (0.26±0.07, 0.56±0.09) (all P<0.01). The healthy PM2.5 group (0.44±0.06, 0.77±0.07) and asthma PM2.5 group (1.33±0.23, 1.25±0.18) were higher than the control group (all P<0.01). Airway remodeling related molecules α-SMA, TGF-β1 and Col-Ⅰ protein in the asthma group (0.60±0.04, 0.52±0.09, 0.36±0.04) were significantly higher than those in the healthy control group (0.31±0.03, 0.22±0.04, 0.23±0.04) (all P<0.01). The health PM2.5 group (0.49±0.02, 0.30±0.03, 0.28±0.03) and the asthma PM2.5 group (0.88±0.09, 0.62±0.03, 0.49±0.07) were higher than the control group (P<0.05 or P<0.01), respectively. The content of HYP in lung tissue of the asthma group (57.71±7.60) μg/100mg was significantly higher than that of healthy control group (40.53±5.73) μg/100mg. The healthy PM2.5 group (53.92±6.82) μg/100mg and asthma PM2.5 group (70.96±4.44) μg/100mg were higher than the control group (P<0.01), respectively. In asthma group and asthma PM2.5 group, the expression of Notch1 and Hes1 protein was positively correlated with the total airway wall area, airway smooth muscle area, collagen deposition area, α-SMA, TGF-β1, Col-Ⅰ and HYP (all P<0.01). Conclusion  PM2.5 can promote early airway remodeling in asthma, and the activation of Notch signaling pathway may be involved in the promoting effect of PM2.5 on early airway remodeling.

Citation: WU Jirong, HE Zhen, ZENG Xiaoli, BAO Hairong, LIU Xiaoju. Effects of fine particulate matter on airway remodeling and Notch signaling pathway in asthmatic mice. Chinese Journal of Respiratory and Critical Care Medicine, 2022, 21(4): 274-281. doi: 10.7507/1671-6205.202202004 Copy

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