OBJECTIVE To clarify the therapeutic effect of Qingfei oral liquid on radiation-induced pulmonary fibrosis(RIPF) and explore its potential mechanism of action.

METHODS SD rats were randomly divided into control group, model group, dexamethasone group and Qingfei oral liquid group. The RIPF model was established by chest radiation exposure. Rats in dexamethasone group and Qingfei oral liquid group were given the corresponding drugs daily by intragastric administration. After 8 weeks, the degree of pulmonary fibrosis was detected by magnetic resonance imaging; lung tissue morphology and collagen deposition were observed by hematoxylin-eosin staining and Masson staining; the levels of TGF-β1 in alveolar lavage fluid, as well as the level of malondialdehyde and the activity of superoxide dismutase in serum, were detected by ELISA; the hydroxyproline content in lung tissue was detected by kit. Human alveolar type Ⅱ epithelial cells(AT2) were treated with radiation and then intervened with Qingfei oral liquid. CCK-8 was used to detect cell viability, Western blotting and ELISA were used to detect pyroptosis markers. After radiation exposure, AT2 cells were co-cultured with human embryonic lung fibroblast(MRC-5) and human bronchial epithelial cells(Beas-2b), respectively. The activation of fibroblasts and the expression of epithelial-mesenchymal transition markers were detected by Western blotting. The active components of Qingfei oral liquid in lung tissue were analyzed, and its underlying mechanisms in treating RIPF was analyzed by network pharmacology.

RESULTS Qingfei oral liquid significantly alleviated radiation-induced lung inflammation, collagen deposition, and fibrosis progression, and the effect was similar to dexamethasone. Qingfei oral liquid significantly inhibited radiation-induced pyroptosis in AT2 cells and reduced the release of inflammatory factors. Co-culture with radiation-treated AT2 cells induced the activation of MRC-5 cells and the mesenchymal transition of Beas-2b cells. Network pharmacological analysis suggested that the mechanism of action of Qingfei oral liquid might be related to the regulation of signaling pathways such as TNF and NOD-like receptors.

CONCLUSION Qingfei oral liquid may inhibit pyroptosis of AT2 cells through TNF and NOD-like receptor pathways and thereby alleviating RIPF.