Study Of Inhibitory Effects Of Resveratrol On Pulmonary Fibrosis Through TGF-β1/ADAMTS-1Signaling Pathway

Objective To observe the effects of resveratrol (Res) on bleomycin-inducedpulmonary fibrosis in rats, and explore whether the effects are mediated bytransforming growth factor-β1(TGF-β1)/a disintegrin-like and metalloproteinase withthrombospondin type1motif (ADAMTS-1) signaling pathway.Methods Ninety SD rats were randomly divided into control group (n=10), modelgroup (n=40) and intervention group(n=40). Rats in the latter2groups wereintratracheally administered with bleomycin A5to produce pulmonary fibrosis,whereas ones in control group were treated with same volume of normal saline.From the second day, rats in intervention group were intragastrically treated with100mg·kg-1Res, whereas ones in the other groups were treated with normal saline in thesame condition. Ten rats in model and intervention groups were sacrificed on days7,14,28and56while all ones in control group were killed on day56as total control.Serum was separated, Then the pulmonary tissue was removed, and HE staining andMasson staining were performed. The mRNA and protein expression of TGF-β1,ADAMTS-1, collagen type Ⅰ(ColⅠ) and collagen type Ⅲ (Col Ⅲ) was detected byfluorescence real time quantitative PCR and Western blotting respectively.Procollagen type Ⅰcarboxyterminal propeptide (PICP) and procollagen type Ⅲaminoterminal propeptide (PⅢNP) were examined by ELISA.Results The pulmonary inflammation and fibrosis in intervention group wassignificantly improved compared with that in model group (P<0.05). In comparisonwith control group, pulmonary ADAMTS-1mRNA and protein expression wasdecreased (P<0.05) and the mRNA and protein expression of TGF-β1, ColⅠ and ColⅢ as well as serum PICP and PⅢNP concentrations were increased (P<0.05). AfterRes treatment, the mRNA and protein expression of ADAMTS-1at every time pointin intervention group was higher than that in model group (P<0.01), whereas the mRNA and protein expression of TGF-β1, ColⅠ and Col Ⅲ as well as serum PICPand PⅢNP concentrations were lower than those in model group (P<0.01).Conclusion Res possesses anti-pulmonary fibrosis in rats effects throughpromoting degradation of pulmonary ColⅠ and Col Ⅲ via activatingTGF-β1/ADAMTS-1signaling pathway.