title: Peiminine ameliorates bleomycin-induced acute lung injury in rats.
abstract: The aim of this study was to investigate whether or not peiminine inhibits lung inflammation and pulmonary fibrosis in a rat model of bleomycin-induced lung injury. Rats were randomly divided into 4 groups. In 3 groups, intratracheal bleomycin (5 mg/kg) was used to induce acute lung injury, followed by administration of either carboxymethyl cellulose (control group, n=14), dexamethasone (DXS group, n=14) or peiminine (peiminine group, n=10). In the fourth group (sham-operated, n=12), normal saline was instilled instead of bleomycin, followed by administration of carboxymethyl cellulose. Drugs were administered intragastrically for 28 days. Lung sections were stained with hematoxylin and eosin (H&E) and Masson's trichrome, to grade the degree of alveolitis and pulmonary fibrosis. The lung index was calculated as the ratio of lung to body weight. Serum levels of interleukin-4 (IL-4), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were obtained using a radioimmunoassay. Immunocytochemical methods were employed to assess the expression of transforming growth factor-β (TGF-β), connective tissue growth factor (CTGF), NF-κB, extracellular signal-related kinase (ERK1/2), Fas and FasL in lung tissue. Peiminine and DXS significantly reduced alveolar inflammation and pulmonary interstitial inflammation in rats with bleomycin-induced lung injury. These protective effects were associated with significant (P<0.05) decreases in the levels of IFN-γ in serum and of TGF-β, CTGF, ERK1/2, NF-κB and FasL in lung tissue. No effects were observed on serum TNF-α or IL-4. In conclusion, peiminine inhibits lung inflammation and pulmonary fibrosis in a rat model of bleomycin-induced lung injury, by reducing circulating IFN-γ levels and inhibiting signal transduction pathways involving TGF-β, CTGF, ERK1/2, NF-κB and FasL.
authors: Cancer Center, Huai'an First People's Hospital, Huai'an 223300, P.R. China.
authors: Hai
authors: H
authors: Guo
authors: Fuzhi
authors: F
authors: Ji
authors: Baorui
authors: B
authors: Liu
authors: Xiaofei
authors: X
authors: Chen
authors: Jingdong
authors: J
authors: He
authors: Jiening
authors: J
authors: Gong
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D001761:Bleomycin / Q000633:toxicity*; D002595:Cevanes / Q000008:administration & dosage*; D024042:Collagen Type I / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008297:Male; D011014:Pneumonia / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D002595:Cevanes; D024042:Collagen Type I; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; D015847:Interleukin-4; D007371:Interferon-gamma; C047331:peiminine