Effects Of Fei-Xian-Ling-â…¢ On Bleomycin Induced Pulmonary Fibrosis And Its Mechanisms In Mice And Rats

Objective:To study the effects of Fei-Xian-Ling-Ⅲon Bleomycin-induce pulmonary fibrosis in mice and rats and explore its mechanisms.Methods : Mice were randomly divided into 6 groups : normal group,model group,prednisone group and three Fei-Xian-Ling-Ⅲtreated groups. Rats were also randomly divided into 6 groups : normal group,model group,prednisone group and three Fei-Xian-Ling-Ⅲtreated groups. Each group has 10 animals .The pulmonary fibrosis animal model was established by intratracheal administration of bleomycin. On day 2 , each bleomycin group was given Fei-Xian-Ling-Ⅲ,prednisone and normal distilled water respectively. On days 28 after drugs administration,animals in each group were killed and the lungs were harvested for histopathological studies by HE or Masson staining. Furthemore,Dynamic changes of morphologies of tapeⅡalveolar epithelial cells(AEC-Ⅱ)were identified by electron microscopy, and assaying the level of T-AOC,T-SOD,MDA,NOS,·OH and HYP in lung tissue,the lung index was also computed。The expression of TGF-β1,Smad2/3,NF-κB,OPN in the lung tissue were determinated by immunohistochemistry.Results:(1)The biochemical tests of serum showed that the treatment groups of Fei-Xian-Ling-Ⅲsignificantly increased the activity of SOD(P<0.05, P<0.01)and increased the inhibition ability to? OH (P<0.05,P<0.01,P<0.001), reduced the contents of MDA(P<0.05,P<0.01)in pulmonary fibrosis mouse serum; The biochemical tests of the tissue homogenate of mouse lung showed that the treatment group of Fei-Xian-Ling-Ⅲsignificantly improved the levels of T-AOC (P <0.01, P <0.05), increased the inhibition ability to ? OH in lung tissue of pulmonary fibrosis mice(P<0.05,P<0.01),and reduced the contens of MDA and HYP (P<0.05, P<0.01)and the activity of NOS in lung tissue of pulmonary fibrosis mice (P <0.01, P <0.05); Fei-Xian-Ling-Ⅲmay reduce the expression of TGF- Smad2/3 NF-КB protein in the lung tissues of pulmonary fibrosis mice(P< 0.05,P<0.01,P<0.001; The observations of transmission electron microscopy showed that: Fei-Xian-Ling-Ⅲreduced the damage extent ofⅡalveolar epithelial cells in lung of pulmonary fibrosis mice.(2)The biochemical tests of serum showed that the treatment group of Fei-Xian-Ling-Ⅲsignificantly increased the activity of SOD (P <0.001), reduce the contents of MDA in pulmonary fibrosis rats serum (P <0.001);The biochemical tests of the tissue homogenate of rats lung showed that the treatment group of Fei-Xian-Ling-Ⅲsignificantly improve the activity of SOD(P<0.05, P<0.01,P<0.001), increased the inhibition ability to? OH pulmonary fibrosis in lung tissue of rats(P<0.05, P<0.01,P<0.001),and reduce the contens of MDA and HYP (P<0.05, P<0.01,P<0.001) and the activity of NOS in lung tissue of pulmonary fibrosis rats(P <0.001, P <0.05);Fei-Xian-Ling-Ⅲmay reduce the expression of TGF,NF-КB protein in the lung tissues of pulmonary fibrosis rats(P<0.05, P<0.01,P<0.001).(3)The degree and extent of alveolitis and fibrosis in the Fei-Xian-Ling-Ⅲtreatment groups had different degree of ease( P <0.01, P <0.05).Conclusion: Fei-Xian-Ling-Ⅲmay improve alveolitis and fibrosis of experimental pulmonary fibrosis,and it has a preventive effect。Its mechanisms may be associated with that Fei-Xian-Ling-Ⅲinhibits the over-production of the activity of oxygen free radicals and reactive nitrogen free radicals, enhances the organism against oxidative stress, inhibits the protein expression of Smad2/3, NF-κB, TGF-β,OPN.