Effects and mechanism of oxymatrine on bleomycin-induced pulmonary fibrosis in mice
Objective:To investigate the inhibitory effect of oxymatrine on bleomycin-induced pulmonary fibrosis(PF)in mice and explore its mechanism.Methods:A total of 72 mice were divided into control group,model group,high,medium and low dose OMT(10,5,2.5 mg/mL)group,positive group,with 12 mice in each group.The lung coefficient of mice was detected after the model was made and gavage intervention was performed,HE and Masson staining were used to observe the pathological changes of lung tissue,and the content of hydroxyproline(Hyp)was detected.The contents of serum transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),interleukin(IL)-1β and IL-10 were detected by ELISA.The expression of TGF-β1 and α-smooth muscle actin(α-SMA)protein in lung tissue was detected by Western Blot.Lung fibroblasts MRC-5 cells were treated with TGF-β1 for 12 h in vitro,were divided into control group,model group,high and low dose OMT(0.1,0.5 mg/mL)group.Cell viability was detected by MTT assay.Western Blot was used to determine the expressions of proteins related to TGF-β 1 and α-SMA.Results:Compared with model group,lung coefficient on day 21 and serum levels of TGF-β 1,IL-1β and TNF-α on day 7,21 were decreased in the high dose OMT group,while IL-10 level was increased(P＜0.05,P＜0.01),the content of HYP in lung tissue was decreased(P＜0.05),and the expressions of TGF-β1 and α-SMA were down-regulated(P＜0.05).Compared with model group,the survival rate of MRC-5 induced by TGF-β1 was inhibited in low and high dose OMT groups(P＜0.05),the protein expression of TGF-β1 and α-SMA in MRC-5 were down-regulated(P＜0.05).Conclusion:OMT may play a role in the treatment of PF by inhibiting the differentiation of lung fibroblasts,regulating the release of inflammatory cytokines,and down-regulating TGF-β1 and α-SMA protein expression.
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