Effect of prednisone on transforming growth factor-β1, connective tissue growth factor, nuclear factor-κBp65 and tumor necrosis factor-α expression in a murine model of hepatic sinusoidal obstruction syndrome induced by Gynura segetum.
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OBJECTIVE
One major cause of hepatic sinusoidal obstruction syndrome (HSOS) is the consumption of products containing pyrrolizidine alkaloids (PA). As the use of herbal preparations has increased in China, so has the number of reports of HSOS induced by ingesting PA-containing herbs. The aim of the present study was to investigate the mechanisms by which prednisone and the related factors, transforming growth factor (TGF)-β1 and connective tissue growth factor (CTGF), prevent liver fibrosis and the pathogenesis of HSOS.
METHODS
A murine model of HSOS was created by oral gavage with Gynura segetum with or without prednisone for 30 days. Histological changes in liver tissue were evaluated by a scoring system in tissue slices subjected to hematoxylin-eosin and Masson trichrome staining. Hepatic expression of TGF-β1 and CTGF mRNA and protein was detected by immunohistochemistry, reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. RT-PCR was also used to detect tumor necrosis factor (TNF)-α and nuclear factor (NF)-κBp65 mRNA expression. Activation of NF-κBp65 was detected by immunohistochemistry.
RESULTS
Intervention with prednisone diminished the symptoms of HSOS in mice treated with G. segetum. Prednisone treatment significantly inhibited expression of TGF-β1 and CTGF mRNA and protein (P < 0.05), and inhibited expression of TNF-α and NF-κBp65 mRNA (P < 0.05) in the liver tissue of HSOS mice.
CONCLUSIONS
Prednisone suppresses the development of liver fibrosis in HSOS mice by inhibiting TGF-β1, CTGF, TNF-α and NF-κBp65 expression.
