Antioxidant and anti-inflammation effect of GHK-Cu in bleomycin-induced pulmonary fibrosis
EUROPEAN RESPIRATORY JOURNAL(2018)
Abstract
Objective: To explore the therapeutic effects of GHK-Cu on BLM-induced pulmonary fibrosis in the mouse model. Methods: Oropharyngeal aspiration of 3mg/kg bleomycin were administered to induce pulmonary fibrosis in C57BL/6 mice. GHK-Cu complex at doses of 0.2ug/g/day, 2ug/g/day and 20ug/g/day was administered intraperitoneally from the 4th day on after the administration of bleomycin. Mice were euthanized on 21th day after administration of BLM. Chronic inflammatory index was used to assess the histological changes. TNF-ɑ and IL-6 level and MPO activity in BALF was measured, MMP-9 and TIMP-1 expression was measured in the lung tissue. The collagen deposition was evaluated by Masson’s staining, Sirius Red Total Collagen detection and hydroxyproline(HYP) assay. Besides, the epithelial to mesenchymal transition(EMT) was evaluated in the lung tissue by the expression of ɑ-SMA and fibronectin. The NF-κB, Nrf2 and TGF-β1/Smad2/3 signaling pathway was detected by western blotting. Results: GHK-Cu complex restored the pathological changes induced by bleomycin. GHK-Cu alleviated the levels of TNF-ɑ and IL-6 in BALF, as well as the MPO activity, meanwhile it reduced the collagen deposition. GHK-Cu significantly improved the MMP-9/TIMP-1 imbalance in the lungs and prevented EMT partially. Furthermore, GHK reversed BLM-induced increases in NF-κB, TGF-β1 and the phosphorylation of Smad2/3, while increased the level of Nrf2 as the antioxidant defense. Conclusions: GHK-Cu attenuates the bleomycin induced inflammation and fibrosis in mouse model by downregulating the NF-κB and activating the Nrf2 expression, thus alleviates collagen deposition and EMT, and suppresses TGF-β1/Smad2/3 signaling.
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Key words
pulmonary fibrosis,antioxidant,anti-inflammation,bleomycin-induced
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