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: Hai Guo, Fuzhi Ji, Baorui Liu, Xiaofei Chen, Jingdong He, Jiening Gong
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 7 Issue 4 Pg. 1103-10 (Apr 2013) ISSN: 1791-3004 [Electronic] Greece
• PMID: 23404624 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cevanes
• Collagen Type I
• Transforming Growth Factor beta1
• Tumor Necrosis Factor-alpha
• Bleomycin
• Interleukin-4
• Interferon-gamma
• peiminine

Topics

• Acute Lung Injury (blood, chemically induced, drug therapy)
• Animals
• Bleomycin (toxicity)
• Cevanes (administration & dosage)
• Collagen Type I (blood)
• Interferon-gamma (blood)
• Interleukin-4 (blood)
• Male
• Pneumonia (blood, chemically induced, pathology)
• Pulmonary Fibrosis (blood, chemically induced, pathology)
• Rats
• Signal Transduction
• Transforming Growth Factor beta1 (blood)
• Tumor Necrosis Factor-alpha (blood)