title: Dihydroartemisinin supresses inflammation and fibrosis in bleomycine-induced pulmonary fibrosis in rats.
abstract: Pulmonary fibrosis is a respiratory disease with a high mortality rate and its pathogenesis involves multiple mechanisms including epithelial cell injury, fibroblast proliferation, inflammation, and collagen coagulation. The treatment regimens still fail to recover this disease. We have previously found that dihydroartemisinin inhibits the development of pulmonary fibrosis in rats. This study aimed to determine the mechanisms of dihydroartemisinin in bleomycin-induced pulmonary fibrosis. The experimental rats were divided into six groups as normal saline control group (NS group), bleomycin group (BLM group), dihydroartemisinin-1, -2, or -3 group (DHA-1, DHA-2 and DHA-3 group) and dexamethasone group (DXM group). In BLM group, rats were treated with intratracheal instillation of bleomycin. NS group received the same volume of saline instead of bleomycin. In DHA-1, DHA-2 and DHA-3 group, in addition to intratracheal instillation of bleomycin, respectively, dihydroartemisinin (25 mg/kg, 50 mg/kg, 100 mg/kg daily) was administrated by intraperitoneal instillation. In DXM group, rats were treated with intraperitoneal instillation of dexamethasone as control. Immunocytochemical assay, reverse transcription PCR and western blot were used for detecting the expression of TGF-β1, TNF-α, α-SMA and NF-κB in lung tissues. What's more, morphological change and collagen deposition were analyzed by hematoxylin-eosin staining and Masson staining. Collagen synthesis was detected by hydroxyproline chromatometry. Results showed that dihydroartemisinin significantly decreased the amount of inflammatory cytokines and collagen synthesis, and inhibited fibroblast proliferation in bleomycin-induced pulmonary fibrosis (P < 0.001). This study provides experimental evidence that dihydroartemisinin could decrease cytokines, alveolar inflammation and attenuates lung injury and fibrosis.
authors.affiliation: College of Basic Medicine, China Medical University China ; College of Basic Medicine, Binzhou Medical University China.
authors.forename: Dongxia
authors.initials: D
authors.lastname: Yang
authors.affiliation: College of Basic Medicine, Binzhou Medical University China.
authors.forename: Wendan
authors.initials: W
authors.lastname: Yuan
authors.affiliation: College of Basic Medicine, Binzhou Medical University China.
authors.forename: Changjun
authors.initials: C
authors.lastname: Lv
authors.affiliation: College of Basic Medicine, Binzhou Medical University China.
authors.forename: Naie
authors.initials: N
authors.lastname: Li
authors.affiliation: College of Basic Medicine, Binzhou Medical University China.
authors.forename: Tongshen
authors.initials: T
authors.lastname: Liu
authors.affiliation: College of Basic Medicine, Binzhou Medical University China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: College of Basic Medicine, Binzhou Medical University China.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Sun
authors.affiliation: College of Basic Medicine, China Medical University China.
authors.forename: Xueshan
authors.initials: X
authors.lastname: Qiu
authors.affiliation: College of Basic Medicine, Binzhou Medical University China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D037621:Artemisinins / Q000627:therapeutic use*; D001761:Bleomycin; D005355:Fibrosis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000199:Actins; D037621:Artemisinins; D001761:Bleomycin; D016328:NF-kappa B; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C498862:Acta2 protein, rat; C039060:artenimol
keywords: Dihydroartemisinin; bleomycin; collagen; pulmonary fibrosis; rats