Based on SLC7A11/GPX4 signaling pathway, the mechanism of inhibiting cell iron death in the treatment of asthma was investigated
Abstract
Objective: To investigate the effects of Pingchuanning prescription (PCN) and Ferrostatin 1 inhibitors on airway inflammation in asthmatic rats from the perspective of cell iron death. Methods: Seventy SD rats were randomly divided into 7 groups: normal group, model group, Pinbuening group, Ferrostatin 1 inhibitor group, Pinbuening + Ferrostatin 1 inhibitor group, dexamethasone group, and Guilong Kechuanning group. 10% chicken egg albumin (OVA) was sensitized by peritoneal and limb subcutaneous injection. The asthmatic rat model was stimulated by 2% OVA atomization combined with cold (2–4 ℃) air stimulation. Pingchuanning (6.43 g/kg), Ferrostatin-1 (10 mg/kg), Pingchuanning (6.43 g/kg) + Ferrostatin-1 (2.5 μmol/kg), dexamethasone (0.5 g/kg), Guilong Kecchuanning (10g/kg) by gavage and atomization, Continuous intervention for 3 weeks. After the last stimulation, the lung tissues of rats were stained with hematoxylin-eosin (H&E) to observe airway inflammation and cell proliferation. The contents of IL-10, IL-22, IL-33 and ALOX15 in serum and LF of asthma were detected by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was used to detect the mRAN expression levels of SLC7A11 and GPX4, and Western blot was used to detect the protein expression levels of SLC7A11 and GPX4. Results: Compared with blank group, the diet, body weight, emotional irritability, respiratory shortness, airway inflammatory cell infiltration, goblet cell hyperplasia, serum and serum LF IL-10, IL-22, IL-33, ALOX15 inflammatory factors increased significantly in model group. The mRNA and protein expression levels of SLC7A11 and GPX4 were decreased. Compared with the model group, the diet of the rats in the Pinbuening, Ferrostatin 1 inhibitor and Pinbuening +Ferrostatin 1 inhibitor groups was gradually improved, wheezing was relieved, and airway inflammatory cell infiltration was significantly reduced. IL-10, IL-22, IL-33 and ALOX15 inflammatory factors in serum and LF of asthma were decreased (P < 0.001), while the mRNA and protein expressions of SLC7A11 and GPX4 were promoted (P < 0.005). Conclusions: Pinbuterin and its Ferrostatin 1 inhibitors can significantly improve airway inflammation induced by OVA combined with cold stimulation in asthmatic rats, and are related to SLC7A11/GPX4 signaling pathway and cell iron death. The efficacy of Pinbuterin combined with Ferrostatin 1 inhibitors is more obvious. It is suggested that the effect of combined treatment is better than that of single compound or western medicine.
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