Triptolide Suppresses Paraquat Induced Idiopathic Pulmonary Fibrosis By Inhibiting TGF?1-Dependent Epithelial Mesenchymal Transition

Part ? Therapeutic effect of triptolide on paraqua-induced pulmonary fibrosisOBJECTIVE: Evaluation of the therapeutic effect of triptolide on pulmonary fibrosis induced by paraqua using animal experiment.METHODS: The paraquat induced pulmonary fibrosis model was adopted to evaluate the effect of TPL on pulmonary fibrosis.The weight of mice and the content of collagen in lung tissue were determined.Lung tissue sections were scored according to degree of inflammatory cell infiltration and pulmonary interstitial fibrosis to evaluate the therapeutic effect of triptolide on pulmonary fibrosis.The effects of triptolide on EMT markers were also studied by immunohistochemistry method.RESULTS: Triptolide can improve the survival state of lung fibrosis mice and reduce lung coefficient,lung tissue collagen percentage and pulmonary fibrosis histopathological score of lung fibrosis model mice induced by paraquat.The key cytokines,such as TGF-?1,TNF-? were significantly increased in paraquat-induced pulmonary fibrosis and TPL have certain therapeutic effect on paraquat-induced pulmonary fibrosis.Triptolide significantly reduced the expression of Vimentin and ?-SMA in the lung tissue of mice with pulmonary fibrosis,increasing the expression of epithelial markers and inhibiting the epithlial to mesenchymal transition(EMT)process.CONCLUSION: Triptolide has a therapeutic effect on paraquat induced pulmonary fibrosis and inhibit the EMT.Part ? Study on the molecular mechanism of triptolide in the treatment of pulmonary fibrosisOBJECTIVE: To elucidate the molecular mechanism of triptolide on the treatment of pulmonary fibrosis: to study the effect of TPL on EMT and the target protein and downstream signaling pathways influenced by TPL.METHODS: In this study,scratch test,transwell experiment,immunofluorescence and other methods were used to study the effect of triptolide on PQ-induced EMT in lung epithelial cells.The effects of triptolide and its possible target TGF-?1 were verified using Biacore method.Furthermore,the effect of triptolide on the EMT induced by TGF-?1 was further verified by immunohistochemistry and western-blot in vitro and in vivo.It is demonstrated that triptolide targets TGF-?1 to play an antipulmonary fibrosis effect.RESULTS: TPL can significantly inhibit PQ-induced migration and invasion of lung epithelial cells and inhibit its induction of EMT;TPL and lung fibrosis inducer TGF-?1 have good binding activity;TPL can inhibit TGF-?1-induced EMT process,TPL inhibits pulmonary fibrosis through regulating the TGF-?1/Smad3 signaling pathway.CONCLUSION: Triptolide can inhibit the pulmonary fibrosis by targeting the TGF-?1/ Smad3 signaling pathway to inhibit EMT of the lung epithelial cells.Part ? Therapeutic effect of triptolide on BLM-induced pulmonary fibrosisOBJECTIVE: Evaluation of the therapeutic effect of triptolide on idiopathic pulmonary fibrosis induced by bleomycin using animal experiment.METHODS: The bleomycin induced pulmonary fibrosis model was adopted to evaluate the effect of TPL on pulmonary fibrosis.The weight of mice and the content of collagen in lung tissue were determined.Lung tissue sections were scored according to degree of inflammatory cell infiltration and pulmonary interstitial fibrosis to evaluate the therapeutic effect of triptolide on pulmonary fibrosis.RESULTS: Triptolide can improve the survival state of lung fibrosis mice and reduce lung coefficient,lung tissue collagen percentage and pulmonary fibrosis histopathological score of lung fibrosis model mice induced by bleomycin.CONCLUSION: Triptolide has a therapeutic effect on bleomycininduced pulmonary fibrosis.