Protective Effects And Molecular Mechanisms Of MMF Against Bleomycin-induced Pulmonary Fibrosis Of Mice

Objective To probe into the protective effects and molecularmechanisms of Mycophenolate mofetil(MMF) in bleomycin(BLM)-inducedpulmonary fibrosis of mice.Methods36mice were randomly divided into6groups(6mice ineach group), including normal control group, MMF control group, BLMmodel group and MMF treatment groups which were consist of low, mediaand high dose. One day after intratracheally instilled BLM(6mg/kg) whichwas dissolved in saline in BLM model group and MMF treatment groups,MMF was given orally in MMF control group (100mg/kg) and MMFtreatment groups(20,60,100mg/kg) once daily for two weeks. All mice werekilled two weeks later, and lung tissues were collected for the followingexperiments. Pulmonary fibrosis was evaluated by Ashcroft score in HE andmasson trichrome stain.The expression of transforming growthfactor-β1(TGF-β1）, COL1A1and COL1A2mRNA were determined byRT-PCR. TGF-β1protein was analyzed by immunohistochemistry and Western blot.Results BLM-induced pulmonary fibrosis model was successfullyconstructed. The degree of fibrosis, expression of TGF-β1(P<0.05),COL1A1and COL1A2mRNA (P<0.01) as well as the TGF-β1protein(P<0.05) in high dose MMF treatment group decreased comparedwith BLM group. No statistic differences were found between the otherMMF treatment groups and BLM model group, MMF control group andnormal control group(P>0.05).Conclusions MMF markedly ameliorated bleomycin-inducedpulmonary fibrosis as well as decreased COL1mRNA expression, whichmaybe associated with down-regulation of TGFβ1in lung tissues.