To investigate and analyze the protective effect of triptolide (TPL) on bleomycin (BLM)-induced pulmonary fibrosis in mice induced by integrin-mediated extracellular matrix remodeling.

Sixty male C57BL/6 mice were randomly divided into control group, model group, dexamethasone group (DXM group), TPL low and high dose groups, with 12 mice in each group. Blood gas analysis was performed in whole blood of abdominal aorta, oxygen partial pressure (PO₂) and blood oxygen saturation (SO₂) were recorded, the pulmonary histology was observed by HE staining, and the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in mice sample in each group were detected. The interaction between triptolide and integrin β1 (ITG-β1) was confirmed by cell thermal migration assay (CESTA) and surface plasmonresonance assay (SPR), and the relative expression levels of ITG-β1, transforming growth factor-β1 (TGF-β1) and Smad3 were detected by Western blot.

The lung tissue integrity of mice in TPL low and high dose groups and DXM group was better, and the interstitial expansion of the lungs was reduced in these groups. At the same time, it was observed that the loss and fusion between the alveoli of the mice in TPL groups and DXM group were repaired, and the samples did not show significant interstitial inflammatory infiltration, effectively alleviating fibrosis. Compared with those in the control group, the levels of PO₂, SO₂, SOD and GSH-Px in the model group were significantly decreased, and MDA content was significantly increased (P<0.01). Compared with those in the model group, the levels of PO₂, SO₂, SOD and GSH-Px in the DXM group, TPL low and high dose groups were significantly increased, while the content of MDA was significantly decreased (P<0.05). Compared with those in the TPL low dose group, the effect of TPL high dose group was more obvious, and the levels of PO₂, SOD and GSH-Px were increased more significantly (P<0.05). The results of CESTA and SPR experiments indicated that triptolide interacted with ITG-β1 and was a possible anti-pulmonary fibrosis target. Compared with those of the control group, the protein expression levels of ITG-β1, TGF-β1 and Smad3 in lung tissue of the model group were increased (P<0.01). The protein expression levels of ITG-β1, TGF-β1 and Smad3 in lung tissue of mice in the DXM group, TPL low and high dose groups were lower than those in the model group (P<0.05), and compared with those in the DXM group and TPL low dose group, the protein expression levels of ITG-β1, TGF-β1 and Smad3 in lung tissue of mice in the TPL high dose group were decreased (P<0.05).

TPL can protect pulmonary fibrosis induced by bleomycin through extracellular matrix remodeling mediated by integrin, and the fibrosis-related change protein induced by integrin can be used as the target of TPL in the treatment of pulmonary fibrosis.