| Objective To study the effect of sinomenine on bleomycin-induced pulmonary fibrosis in mice and its possible mechanism.Methods180mice were randomly divided into six groups(each group has30mice):a normal control group(group A), a lung fibrosis group(group B), a dexamethasone group(groupC.2mg/kg), a low-dose sinomenine group(gropuD,40mg/kg) and a high-dose sinomenine group(groupE,80mg/kg), a N-acetylcysteine group(groupF,50mg/kg). The mice model of pulmonary fibrosis in the B, C, D, E, F group Were intratracheally injected with bleomycin hydrochloride(5mg/kg). Normal control mice received the same volume of intratracheal saline instead of bleomycin, and then the mice of A and B group received oral saline, C, D, E, F group received oral relevant medications. Ten rats of each group were sacrificed7,14and28days after intratracheal instillation. The bronchoalveolar lavage fluid (BALF) were gotten and the cells counting as well as differentiation were figured out; Right lung tissue samples were harvested for histopatology:HE and MASSON stain were done to observe the extent of alveolitis and fibrosis of lung tissue respectively, and measured protein levels of transforming growth factor-β1(TGF-β1) and α-smooth muscle actin (α-SMA) by Histoimmunochemical method; Left lung samples were harvested to made homogenate for measured the expression of TGF-β1mRNA, a-SMAmRNA and measure the content of HYP, MDA, MPO, TAC.Results (1) The total cell number and the proportion of neutrophils in group B were significantly higher than those in group A,and lower than those in group C, D, E, F at day7,14,28. And the parameters in group D, E, F were still higher than those in group C at day7and14. There were no differences in group C, D, E, F at day28(F=161.25,74.21,72.39,80.67,33.24,148.27, P all<0.01).(2) the scores of alveolitis and pulmonary fibrosis in group B were significantly higher than that in group A, and lower than that in group C, D, E, F at day7,14,28. These index in group D, E, F at day7,14were higher than that in group C. there were no differences among group C, D, E, F on scores of alveolitis at day28and scores of pulmonary fibrosis at day7,14,28(F=97.06,114.44,53.64.43.40,33.30,92.49, P all<0.01).(3) The expression of TGF-β1mRNA and α-SMA mRNA at day7.14.28in group B were remarkably increased than those in group A, and decreased than those in group C, D, E, F (F=142.51,57.25,27.66,50.27,41.09,5.62, P all<0.01). The proteins levels of TGF-β1and α-SMA at day7,14,28in group B were remarkably increased than those in group A, and decreased than those in group C, D, E,F(F=8.42,32.07,62.49,33.73,105.62,246.83, Pall<0.01). Among group C, D, E, F there were no differences on these parameters at all time points.(4)The level of HYP at day7,14,28in group B were higher than those in group A, and were lower than that in group C. The level of HYP in group D, E, F at day14,28were lower than that in group B, but higher than that in group C at day7,14(F=118.39,41.72,61.55, P<0.01, P<0.05). Among group C, D, E, F there were no differences on these parameters at day of28.(5) The level of TAC at day7,14,28in group B were lower than those in group A, The level of TAC in group C, D, E, F at day7,14were higher than that in group B(F=54.85,50.93,11.35, P<0.01), Among group C, D, E, F there were no differences on these parameters at all time points.(6) The level of MDA at day7,14,28in group B were higher than those in group A, and lower than those in group C, D, E, F(F=518.62,335.01,49.98, P all <0.01), Among group C, D, E, F there were no differences on these parameters at all time points.(7) The level of MPO at day7,14,28in group B were higher than those in group A, The level of MPO in group C, D, E, F at day7,14were lower than that in group B(F=300.92,238.29,1.44, P<0.01, P<0.05), Among group C, D, E, F there were no differences on these parameters at all time points.Conclusion sinomenine can reduce bleomycin-induced lung damage and the signal transduction of TGF-β1and α-SMA may be involved. |
PDF Full Text Request