To investigate the effects of celastrol (Cel) on airway remodeling factors, collagen synthesis and degradation in lung fibroblasts of chronic obstructive pulmonary disease (COPD) rats by regulating the neurogenic locus notch homolog protein (Notch) pathway.

A total of 30 rats were randomly divided into 3 groups: animal control group (normal feeding), animal model group (COPD rat model established by smoke exposure combined with lipopolysaccharide tracheal instillation) and animal experimental group (intraperitoneal injection of 0.01 mg·kg^-1 Cel after successful modeling). The bronchial fibroblasts (BF) cells were isolated from rats in the animal model group and randomly divided into cell control group (no treatment), cell experimental group (2 μmol·L^-1 Cel) and inhibitor group [1 mmol·L^-1 valproic acid (VPA)]. Pulmonary function was assessed in rats using invasive pulmonary function testing methods; Western blot was used to detect the expression of Notch signaling pathway-related proteins in each group of cells; real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect mRNA expression of airway remodeling-related factors; enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of matrixmetalloproteinase-1 (MMP-1) and tissue inhibitors of metalloproteinase-1 (TIMP-1) in each group of cells.

The forced vital capacity (FVC) of rats in animal control group, animal model group and animal experimental group were (6.74±0.87), (3.28±0.51) and (4.94±0.83) mL, respectively; the forced expiratory volume in 0.1 second (FEV0.1) were (3.94±0.45), (1.05±0.16) and (2.41±0.37) mL, respectively; the peak expiratory flow (PEF) were (28.09±4.60), (16.63±3.21) and (21.55±4.02) L·min^-1, respectively. Significant differences were observed in the above indicators between animal control group and animal model group, and between animal model group and animal experimental group (P<0.01, P<0.001). The relative expression levels of (Notch1) protein in cell control group, cell experimental group and inhibitor group were 1.00±0.19, 0.12±0.02 and 0.38±0.06, respectively; the relative expression levels of Notch1 receptor intracellular binding domain (NICD1) protein were 1.00±0.17, 0.72±0.12 and 0.85±0.13, respectively; the relative expression levels of serrated typical Notch ligand 1 (Jagged1) protein were 1.00±0.15, 0.71±0.11 and 0.84±0.12, respectively; the relative expression levels of hair and enhancer of split 1 (Hes1) protein were 1.00±0.11, 0.69±0.08 and 0.81±0.09, respectively; the relative expression levels of MMP-9 mRNA were 1.00±0.16, 0.59±0.08 and 0.73±0.11, respectively; the relative expression levels of type Ⅰ collagen(ColⅠ) mRNA were 1.00±0.14, 0.67±0.09 and 0.86±0.14, respectively; the relative expression levels of α-smoth muscle actin (α-SMA) mRNA were 1.00±0.16, 0.41±0.07 and 0.78±0.13, respectively; the relative expression levels of transforming growth factor-β (TGF-β) mRNA were 1.00±0.18, 0.53±0.09 and 0.75±0.14, respectively; the contents of MMP-1 were (1.19±0.17), (0.80±0.15) and (1.06±0.15) ng·mL^-1, respectively; the contents of tissue inhibitor of protease-1 (TIMP-1) were (219.78±30.24), (131.94±18.15) and (167.51±21.01) ng·mL^-1, respectively. There were all statistically significant differences in the above indicators between cell control group and cell experimental group, as well as between cell experimental group and inhibitor group (P<0.05, P<0.01, P<0.001).

Celastrol can effectively improve lung function and pulmonary pathological damage in COPD rats, reduce the levels of inflammatory cells and inflammatory factors, and improve the imbalance of airway remodeling-related factors and collagen synthesis/degradation in BF cells, which may be related to its inhibition of Notch signaling activation.