Total glucosides of Danggui-Buxue-Tang attenuates bleomycin-induced pulmonary fibrosis via inhibitio

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<正>Danggui-Buxue-Tang(DBT) is a famous traditional Chinese formula.We have reported that total glucosides of Danggui-Buxue-Tang(DBTG) can attenuate bleomycin-induced lung fibrosis through reduction of pro-inflammatory cytokines or the decrease of I collagen accumulation.The present study we further focuses on investigating mechanisms underlying the anti-fibrosis effects of DBTG on pulmonary fibrosis(PF) rats.Animals were randomly divided into six groups:(1) saline control group;(2) Bleomycin group in which rats were intratracheally instillated with bleomycin(5mg/kg);(3-5) Bleomycin and DBTG group,in which DBTG were given to rats daily(16,32 or 64 mg/kg/day,i.g.) one day after bleomycin instillation for 4 weeks until the end of the treatment;(6) Bleomycin and positive control group. Bleomycin stimulation resulted in a significant increase in the pathological scores for alveolitis and lung fibrosis and an evident increase in the contents of extracellular matrix(ECM) components in serum including hyaluronic acid(HA),laminin(LN), procollagen typeⅢ(PCⅢ) and collagenⅣ(CⅣ).Moreover,bleomycin-induced pulmonary injury and lung fibrosis was indicated by increased lung MMP-1,MMP-9 and TIMP-1 mRNA levels.On the other hand,DBTG treatment attenuated bleomycin-induced alveolitis and lung fibrosis,significant decreased the concentrations of HA,LN,PCⅢand CⅣin serum.Furthermore,administration of DBTG resulted in a significant reduction in metalloproteinase-1(MMP-1),MMP-9 and the tissue inhibitor of metalloproteinase-1(TIMP-1) mRNA levels in different stages of pulmonary fibrosis,and the balance between MMPs and TIMPs.Thus,the findings of the present study provide evidence that DBTG inhibits ECM deposition and modulates MMPs and TIMPs expression in the lung tissue,which may be associated with the attenuation of experimental pulmonary fibrosis.
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