Effects Of Fei-Xian-Ling-Ⅰ On Bleomycin Induced Pulmonary Fibrosis And Its Mechanisms In Rodent Model

Objective: The effects of Fei-Xian-Ling-Ⅰ( FXL-Ⅰ) were investigated on bleomycin-induced pulmonary fibrosis in rodent model and its mechanisms.Methods: Kunming mice and Sprague-Dawley rats were randomly divided into six groups:normal control group, BLM model group,positive control prednisolone group and low-, middle-, high-dose FXL-Ⅰgroups. The model for pulmonary fibrosis was replicated by intratracheal administration of bleomycin. Then each group were intragastric corresponding administration from the 2th day, but the normal control group and bleomycin model group were only received sodium carboxymethycellulose. After 28 days the lung tissues were harvested for lung indexes, biochemical measurements, histopathologic study, transmission electron microscope observation and immunohistochemistry study to analyze the expression of transforming growth factorβ1 (TGF-β1), Smad 2/3, collagen typeⅢ(Col-Ⅲ) , Nuclear factor-κB (NF-κB)and caveolin-1(Cav-1) in the fibrosis lung tissue.Results: (1) FXL-Ⅰadministration obviously increased body weight(sP<0.001), significantly reduced lung indexes and HYP contents in pulmonary fibrosis mice and rats compared with those in the model group(P<0.001, P<0.01, P<0.05); (2) biochemical measurements showed FXL-Ⅰelevated SOD activity and the ability of inhibiting·OH, while significantly reduced MDA contents in lung homogenate and serum (P<0.05,P<0.01) in pulmonary fibrosis mice. Moreover, FXL-Ⅰimproved T-AOC and decreased NOS activity (P<0.05,P<0.01) in the lung homogenate of bleomycin-induced pulmonary fibrosis mice. After FXL-Ⅰadministration, T-AOC, SOD activity and the ability of inhibiting·OH dramatically were enhanced (P<0.05,P<0.01,P<0.001), while MDA contents and NOS activity were significantly decreased (P<0.05,P<0.01,P<0.001) in the lung and serum of pulmonary fibrosis rats. In addition, SDH activity in the lung tissue of bleomycin induced rats also obviously increased (P<0.05, P<0.01, P<0.001); (3) The histological scoring of lung specimens and transmission electron microscope observation demonstrated that FXL-Ⅰdramatically alleviated the extent of the alveolitis and pulmonary fibrosis (P<0.05, P<0.01, P<0.001) and improved the pathomorphology and ultrastructure of pulmonary fibrosis rodent model; (4) immunohistochemistry studies revealed that FXL-Ⅰsupplementation down-regulated the levels of TGF-β1,Smad2/3, Col-Ⅲand NF-κB protein in the lung tissue of pulmonary fibrosis mice and rats. In addition, the levels of Cav-1 protein were up-regulated in the lung tissue of pulmonary fibrosis rats (P<0.05, P<0.01, P<0.001).Conclusion: FXL-Ⅰcould alleviate bleomycin-induced pulmonary fibrosis in mice and rats, which might be associated with of anti-inflammation and anti-oxidization, the up-regulated Cav-1 protein expression and down-regulation NF-κB protein expression, inhibiting TGF-β1 /Smads signal transduction pathway to depress the levels of Col-Ⅲprotein and excessive extracellular martrix deposition in lung tissues of bleomycin induced pulmonary fibrosis mice and rats.