Abstract: Objective To investigate the effect of Bufei-Huoxue formula (BFHX) on inflammatory injury in the lung tissue of rat model with chronic obstructive pulmonary disease (COPD). Methods Rat model of COPD was established by endotracheal infusion of lipopolysaccharide (LPS) combined with smoking stimulation. Rats were randomly assigned into model group, positive drug ambroxol (positive) group, low- and high-dose BFHX (BFHX-L, BFHX-H) groups, and high-dose BFHX+SphK1/S1P pathway activator (BFHX-H+PMA) group. The control group consisted of 8 healthy rats. The lung function of rats was examined, and the level of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) was measured by ELISA. The pathological changes of lung tissue were detected by HE staining, bronchial mucus secretion was measured by AB-PAS staining and pulmonary fibrosis was measured by Masson staining. The expression of Muc5ac protein in lung tissue was measured by immuno-histochemistry and the expression of SphK1,S1P,α-SMA,ColⅠ and TGF-β proteins was detected by Western blot. Results Compared with the control group, rats in the model groups exhibited decreased lung function and aggravated pulmonary fibrosis accompanied by elevated level of TNF-α,IL-6,and IL-8 in BALF, increased bronchial mucus secretion and collagen volume fraction,Muc5ac positive expression and protein expression level of SphK1,S1P,α-SMA,ColⅠ,and TGF-β in lung tissue, as well as a reduced level of IL-10(P＜0.05). Compared with the model groups, the BFHX-treated group and positive group showed improved pulmonary function and alleviated histo-pathological damage of lung tissue. Additionally The level of TNF-α,IL-6,and IL-8 in BALF, bronchial mucus secretion in lung tissue, collagen volume fraction, positive expression of Muc5ac,as well as the protein expression of SphK1,S1P,α-SMA, ColⅠand TGF-β were all significantly decreased, while the level of IL-10 was markedly increased(P＜0.05). Compared with BFHX-H group, the BFHX-H+PMA group exhibited aggravated histo-pathological damage and impaired pulmonary function in lung tissue. Furthermore, the levels of TNF-α,IL-6,and IL-8 in BALF,the amount of bronchial mucus secretion in lung tissue collagen volume fraction, the positive expression of Muc5ac,as well as the protein expression levels of SphK1,S1P,α-SMA,ColⅠ,and TGF-β were also significantly increased, but the level of IL-10 was markedly decreased(P＜0.05). Conclusions BFHX alleviates airway mucus hyper-secretion and pulmonary fibrosis in COPD rat models and improve lung tissue inflammatory injury and lung function. Its mechanism of action potentially related to the reduction of SphK1/S1P pathway activity.

Key words: Bufei-Huoxue formula (BFHX), chronic obstructive pulmonary disease, airway mucus, pulmonary fibrosis, SphK1/S1P pathway