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.
ObjectiveTo investigate the effects of chronic Aspergillus fumigatus (AF) exposure on the expression of platelet-derived growth factor (PDGF) and airway remodeling in the asthmatic rats. MethodsForty male Wistar rats were randomly divided into five groups (8 rats per group): group A (control group): sensitized with ovalbumin (OVA) and challenged with saline; group B (bronchial asthma group): sensitized and challenged with OVA to establish a chronic asthma model; groups C-E (bronchial chronic asthma + AF spores inhalation for 1 week, 3 weeks, or 5 weeks): the asthma rats were received intranasal inhalation of Aspergillus fumigatus spores for 1 week (Group C), 3 weeks (Group D), or 5 weeks (Group E). The concentrations of interleukin-5 (IL-5), interleukin-13 (IL-13), and transforming growth factor-beta (TGF-β) in bronchoalveolar lavage fluid (BALF) were measured using enzyme-linked immunosorbent assay (ELISA). Lung sections were stained with periodic acid Schiff (PAS) and Masson trichrome stain, and the images were analyzed morphometrically.The expression of PDGF were detected by immunohistochemistry and Western blot. ResultsThe levels of TGF-β (66.43 ± 2.78 ng/mL), IL-5 (33.49 ± 2.01 ng/mL), and IL-13 (50.78 ± 2.16 ng/mL) in BALF, as well as the extent of goblet cell hyperplasia (8.82 ± 1.95) and the degree of subepithelial collagen deposition (10.28 ± 2.48) in group B were higher than those in Group A (P<0.05). After inhalation of AF spores, the concentrations of TGF-β, IL-5, IL-13, along with the extent of goblet cell hyperplasia, and the degree of collagen deposition in the airways were increased progressively in group C, group D and group E (P<0.05). The expression of PDGF in the airways were upregulated in a dose-dependent manner. The extent of subepithelial collagen deposition and goblet cell hyperplasia in the airways were positively correlated with the expression of PDGF. ConclusionChronic exposure to Aspergillus fumigatus upregulates the expression of PDGF in the airways of bronchial asthma rats, thereby promoting airway remodeling.
