Search

Pulmonary fibrosis (PF) is a serious chronic lung disease with unknown pathogenesis. Researches have confirmed that oxidative stress which is regulated by NADPH oxidase-4 (NOX4), a main source of reactive oxygen species (ROS), is an important molecular mechanism underlying PF. Previous studies showed that total glucosides of Danggui Buxue Tang (DBTG), an extract from a classical traditional Chinese herbal formula, Danggui Buxue Tang (DBT), attenuated bleomycin-induced PF in rats. However, the mechanisms of DBTG are still not clear. We hypothesize that DBTG attenuates PF through regulating the level of oxidative stress by inhibiting NOX4. And we found that fibrosis indexes hydroxyproline (HYP) and type I collagen (Col-I) were lower in DBTG groups compared with the model group. In addition, the expression of transforming growth factor-β1 (TGF-β1) and expression of alpha smooth muscle actin (α-SMA) were also much more decreased than the model group. For oxidative stress indicators, DBTG blunted the decrease of superoxide dismutase (SOD) activity, total antioxidant capacity (T-AOC), and the increase in malondialdehyde (MDA), 8-iso-prostaglandin in lung homogenates. Treatment with DBTG restrained the expression of NOX4 compared to the model group. Present study confirms that DBTG inhibits BLM-induced PF by modulating the level of oxidative stress via suppressing NOX4.

Objective: This study was to explore the antifibrotic effect and the possible mechanism of total polysaccharides of Yupingfeng (YPF-P) on bleomycin (BLM)-induced pulmonary fibrosis in rats., Methods: Pulmonary fibrosis was induced in Sprague-Dawley rats by BLM (5 mg/kg), killed 14 and 28 days after BLM administration by abdominal aorta exsanguination and removed the lungs. Lung coefficient was counted at the same time. Besides, H&E and Masson's trichrome staining for histopathological changes of lung tissues were observed. Additionally, western blotting and immunohistochemical staining techniques were used to detect expression of transforming growth factor-β1 (TGF-β1), type I collagen (Col-I) and α-smooth muscle actin (α-SMA). Finally, the levels of Col-I and hydroxyproline (HYP) in lung tissues were also utilized., Key Findings: YPF-P alleviated the increase of lung coefficient induced by BLM instillation in pulmonary fibrosis rat, pathologic changes and collagen distribution were obviously ameliorated, while the increase of α-SMA-positive cells and TGF-β1 expression was prevented after YPF-P treatment. Moreover, the contents of HYP and Col-I were decreased in YPF-P group., Conclusions: YPF-P had antifibrotic effect in experiment, which may reduce the synthesis and promote the deposition of Col-I via suppressing the increase of TGF-β1-mediated activation of myofibroblasts., (© 2014 Royal Pharmaceutical Society.)

Objective This study was to explore the antifibrotic effect and the possible mechanism of total polysaccharides of Y upingfeng ( YPF- P) on bleomycin ( BLM)-induced pulmonary fibrosis in rats. Methods Pulmonary fibrosis was induced in Sprague- Dawley rats by BLM (5 mg/kg), killed 14 and 28 days after BLM administration by abdominal aorta exsanguination and removed the lungs. Lung coefficient was counted at the same time. Besides, H&E and Masson's trichrome staining for histopathological changes of lung tissues were observed. Additionally, western blotting and immunohistochemical staining techniques were used to detect expression of transforming growth factor-β1 ( TGF-β1), type I collagen ( Col- I) and α-smooth muscle actin (α- SMA). Finally, the levels of Col- I and hydroxyproline ( HYP) in lung tissues were also utilized. Key findings YPF- P alleviated the increase of lung coefficient induced by BLM instillation in pulmonary fibrosis rat, pathologic changes and collagen distribution were obviously ameliorated, while the increase of α- SMA-positive cells and TGF-β1 expression was prevented after YPF- P treatment. Moreover, the contents of HYP and Col- I were decreased in YPF- P group. Conclusions YPF- P had antifibrotic effect in experiment, which may reduce the synthesis and promote the deposition of Col- I via suppressing the increase of TGF-β1-mediated activation of myofibroblasts. [ABSTRACT FROM AUTHOR]

Epithelial–mesenchymal transition (EMT) is a complex biological program during which cells loss epithelial phenotype and acquire mesenchymal features. EMT is thought to be involved in the pathogenesis of various fibrotic diseases including pulmonary fibrosis (PF). Recent studies suggest that endoplasmic reticulum (ER) stress is associated with EMT in the progression of PF. However, the exact mechanism is unclear. Here, we developed a PF model with bleomycin (BLM) administration in rats and conducted several simulation experiments in alveolar epithelial cell (AECs) RLE-6TN to unravel the role of inositol-requiring protein 1 (IRE1) – X-box-binding protein 1 (XBP1) signal pathway in ER stress-induced EMT in PF. First, we observed that ER stress was occurred in type II AECs accompanied by EMT in BLM-induced PF. Then we explored the role of IRE1-XBP1-snail pathway in transforming growth factor (TGF)-β1/tunicamycin (TM)-induced EMT. When TGF-β1/TM was treated on AECs, IRE1 and XBP1 were overexpressed, meanwhile, snail expression was upregulated accompanied with EMT. However, when IRE1 or XBP1 was knockdown, TGF-β1/TM-induced EMT were blocked while the expression of snail was inhibited. Then we silenced snail and found that TGF-β1/TM-induced EMT were also suppressed, but it had no effect on the up-regulated expression of IRE1 and XBP1. Thus, we concluded that IRE1-XBP1 pathway promotes EMT via mediating snail expression in PF. [ABSTRACT FROM AUTHOR]