Abstract:

Objective To observe the inhibitory effect of Huaiqihuang on airway remodeling and collagen deposition in asthmatic rats by regulating airway epithelial cell ferroptosis, and to explore the possible mechanism. Methods Sixty rats were randomly divided into the normal group, the asthma group, the low-dose group, the high-dose group and the high-dose + inhibitor group, with 12 rats in each group. Except for the normal group, asthma models were established in the other groups by ovalbumin (OVA) sensitization and nebulized challenge. Rats with unsuccessful modeling were excluded, and finally 10 rats were included in each group. Rats in the low-dose group and the high-dose group, starting from the day of the first OVA challenge, received daily intragastric administration of Huaiqihuang solution at 3.6 g/kg and 7.2 g/kg, respectively. Rats of the high-dose + inhibitor group received high-dose Huaiqihuang and intraperitoneal injection of sulfasalazine (150 mg/kg). Rats of the normal group and the asthma group received daily intragastric administration of an equal volume of normal saline. Lung function and the contents of malondialdehyde (MDA), glutathione (GSH) and reactive oxygen species (ROS) in lung tissue were compared between groups. HE staining and Masson staining were used to measure the thickness of airway wall, airway smooth muscle and collagen fiber deposition. Western blot assay was used to detect the protein expression of p-Jun/Jun, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in lung tissue. Results Airway resistance (RL), MDA and ROS contents in lung tissue, and p-Jun/Jun ratio were lower in the low-dose group than those in the asthma group, and those in the high-dose group were lower than those in the low-dose group. And those in the high-dose + inhibitor group were higher than those in the high-dose group (all P<0.05). Lung dynamic compliance (Cdyn), GSH content in lung tissue, and protein expression of SLC7A11 and GPX4 were higher in the low-dose group than those in the asthma group, those in the high-dose group were higher than those in the low-dose group, and those in the high-dose + inhibitor group were lower than those in the high-dose group (all P<0.05). The thicknesses of airway wall, airway smooth muscle and collagen fiber deposition were less in the low-dose group than those in the asthma group, those in the high-dose group were less than those in the low-dose group, and those in the high-dose + inhibitor group were greater than those in the high-dose group (all P<0.05). Conclusion Huaiqihuang can inhibit airway remodeling and collagen deposition in asthmatic rats, and its mechanism may be related to the inhibition of Jun activation, up-regulation of SLC7A11 expression, and thereby the alleviation of ferroptosis of airway epithelial cells.

Key words: asthma, ferroptosis, airway remodeling, collagen, proto-oncogene proteins c-jun, solute carrier proteins, Huaiqihuang