• 대한한방소아과학회지
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• 제23권3호
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• pp.233-240
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• 2009

Objectives To evaluate that Okwada affected which factors for treatment of lung fibrosis. Methods Bleomycin induced lung fibrosis model made in mice. After Okwada lyophilized, power sample obtained and melt in distilled water. Okwada solution administered mice through oral route on 21 days after bleomycin instillation and this procedure performed once a day for 7 days. We divided by three groups; normal (control), bleomycin induced lung fibrosis without treatment (experimental), bleomycin induced lung fibrosis with treatment (treatment). On six weeks after bleomycin instillation, mice sacrificed and removed lung. Weperformed Western blot analysis for TGF-beta, phosphodiesterase 5A, interleukin (4,5,13) and compared therapeutic effects of Okwada. Results On western blot analysis, all normal and experimental mice detected TGF-beta, phosphodiesterase 5A, interleukin 4,5,13. The amount of band of TGF-beta, phosphodiesterase 5A, interleukin 5 in experimental and treatment group was similar. However, interleukin 4,13 of treatment group decreased compared with experimental group. Conclusions Okwada would be effected the lung fibrosis through suppression of interleukin 4,13.

• 대한한방내과학회지
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• 제25권1호
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• pp.71-80
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• 2004

Objective : Idiopathic Lung Fibrosis(IPF) is chronic fibrotic interstitial pneumonia. The pathogenesis is unclear. Lonicerae Flos is known to prevent the inflammation and reinforce the immune system. The effects of Lonicerae Flos on bleomycin-induced lung fibrosis is evaluated. Material and Methods: Lonicerae Flos extract was given to the Normal rats, control(bleomycin) rats everyday and treated(bleomycin and lonicerae flos) rats 21.0 mg per body weight 109 for 14 days. 14 days after, we observed the change of leukocyte count and percentage of IFN-gamma and IL-4 in BALF. and that of Semiquantative histological index(SHI). Results : Compared to control rats, Lonicerae Flos decreased leukocyte count(P<0.01) lymphocyte, neutrophil percentage(P<0.05), SHI(P<0.01), IFN-gamma and IL-4(P<0.05) in Treated rats. Otherwise, macrophage percentage was increased(P<0.01) in Treated rats. Conclusion : This study showed that Lonicerae Flos reduced the change of inflammatory cells and cytokines in bleomycin-induced lung fibrosis and reduced the fibrosis of tissue. And, we needed many other distinct researches on lung fibrosis.

• 대한한의학회지
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• 제25권2호
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• pp.41-50
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• 2004

Backgrounds & Objectives: Many acute and chronic lung disorders with variable degrees of pulmonary inflammation and fibrosis are collectively referred to as interstitial lung diseases. Idiopathic pulmonary fibrosis (IPF) is one of several idiopathic interstitial pneumonias with the pathogenesis unclear. Astragali Radix is known to inhibit the Th2 immune response. The effects of Astragali Radix on bleomycin-induced lung fibrosis were evaluated. Materials and Methods: Astragali Radix extract was daily given to the normal rats, control (bleomycin) and treated (bleomycin and Astragali Radix extract, 24.0 mg/10g body weight) rats for 14 days. After 14 days, we observed the change of total leukocyte count and percentage, IFN-gamma and IL-4 in BALF (Bronchoalveolar lavage fluid), and of semiquantitative histological index (SHI). Results: Compared to the control group, Astragali Radix decreased total leukocyte count (p<0.05), lymphocyte (p<0.05), neutrophil (no significance) percentage, SHI (p<0.05), IFN-gamma and IL-4 (p<0.05). Otherwise, macrophage percentage was increased (p<0.01). Conclusion: This study showed that Astragali Radix reduced the incidence of inflammatory cells and cytokines and prevented the fibrosis of tissue in bleomycin-induced lung fibrosis rats.

• Biomolecules & Therapeutics
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• 제27권3호
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• pp.318-326
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• 2019

Sphingosine 1-phosphate (S1P) levels are often found to be elevated in serum, bronchoalveolar lavage, and lung tissue of idiopathic pulmonary fibrosis patients and experimental mouse models. Although the roles of sphingosine kinase 1 and S1P receptors have been implicated in fibrosis, the underlying mechanism of fibrosis via Sphingosine 1-phosphate receptor 2 ($S1P_2$) has not been fully investigated. Therefore, in this study, the roles of $S1P_2$ in lung inflammation and fibrosis was investigated by means of a bleomycin-induced lung fibrosis model and lung epithelial cells. Bleomycin was found to induce lung inflammation on day 7 and fibrosis on day 28 of treatment. On the $7^{th}$ day after bleomycin administration, $S1P_2$ deficient mice exhibited significantly less pulmonary inflammation, including cell infiltration and pro-inflammatory cytokine induction, than the wild type mice. On the $28^{th}$ day after bleomycin treatment, severe inflammation and fibrosis were observed in lung tissues from wild type mice, while lung tissues from $S1P_2$ deficient mice showed less inflammation and fibrosis. Increase in TGF-${\beta}1$-induced extracellular matrix accumulation and epithelial-mesenchymal transition were inhibited by JTE-013, a $S1P_2$ antagonist, in A549 lung epithelial cells. Taken together, pro-inflammatory and pro-fibrotic functions of $S1P_2$ were elucidated using a bleomycin-induced fibrosis model. Notably, $S1P_2$ was found to mediate epithelial-mesenchymal transition in fibrotic responses. Therefore, the results of this study indicate that $S1P_2$ could be a promising therapeutic target for the treatment of pulmonary fibrosis.

• 대한한방내과학회지
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• 제26권1호
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• pp.169-181
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• 2005

Background & Objective : Idiopathic Lung Fibrosis(IPF) is chronic fibrotic interstitial pneumonia. The pathogenesis is unclear. Fritillariae Rhizoma is the most commonly used antitussive and expectorant Oriental medicinal herb. The effects of Fritillariae Rhizoma on bleomycin-induced lung fibrosis is here evaluated. Material and Methods : Fritillariae Rhizoma extract was daily given to the normal rats, control(bleomycin) rats and treated(bleomycin and Fritillariae Rhizoma) rats at 9.0 mg per body weight 10g for 14 days. 14 days later, the change in Leukocyte count and percentages were observed, as well as IFN-gamma and 1L-4 in BALF, and the change in Semiqualitative histological index(SHI). Results : Compared to control rats, Fritillariae Rhizoma treated rats showed a lower leukocyte count(P<0.05) lymphocyte, neutrophil percentage, SHI(p<0.05), IFN-gamma and IL-4(p<0.05) in treated rats. Conversely, macrophage percentages went higher(p<0.05) in treated rats. Conclusion : This study supports a role for Fritillariae Rhizoma in reducing the maintaining inflammatory cells and cytokines in rats with bleomycin-induced lung fibrosis and in the reduction of fibrosis tissues. Further research is needed in order to develop an effective treatment for lung fibrosis.

• 대한한방소아과학회지
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• 제23권3호
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• pp.217-231
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• 2009

Objectives To evaluate that Okwada affected which factors for treatment of lung fibrosis. Methods Bleomycin induced lung fibrosis model made in mice. After Okwada lyophilized, power sample obtained and melt in distilled water. Okwada solution administered mice through oral route on 21 days after bleomycin instillation and this procedure performed once a day for 7 days. We divided by three groups; normal (control), bleomycin induced lung fibrosis without treatment (experimental), bleomycin induced lung fibrosis with treatment (treatment). On six weeks after bleomycin instillation, mice sacrificed and removed lung. We performed Western blot analysis for TGF-beta, phosphodiesterase 5A, interleukin (4,5,13) and compared therapeutic effects of Okwada. Results On western blot analysis, all normal and experimental mice detected TGF-beta, phosphodiesterase 5A, interleukin 4,5,13. The amount of band of TGF-beta, phosphodiesterase 5A, interleukin 5 in experimental and treatment group was similar. However, interleukin 4,13 of treatment group decreased compared with experimental group. Conclusions Okwada would be effected the lung fibrosis through suppression of interleukin 4,13.

• 대한한방소아과학회지
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• 제22권2호
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• pp.37-49
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• 2008

Objectives : Idiopathic pulmonary fibrosis (IPF) is chronic fibrotic interstitial pneumonia and the pathogenesis is unknown. Peucedani Radix is well-known for the treatment of respiratory diseases and pulmonary hypertension. This study was to evaluate the effectiveness of Peucedani Radix on the bleomycin-induced lung fibrosis model (BLFM) in mouse. Methods : We induced lung fibrosis by intratracheal instillation of bleomycin in C57BL/6J. We compared two groups BLFM without Peucedani Radix (group I) and BLFM with Peucedani Radix (group II). We performed bronchoalveolar lavages (BAL) and obtained lung specimens from both group I and II on the 7th (A) and 21st (B) day, and also for the normal group. We compared with group I and II to find BAL by using ANOVA test and to find pathologic symptoms by using semiquantitative histological index (SHI). Results : In BAL, total cell counts, lymphocytes, and neutrophils was increased in both group I and II comparing with normal group. However, lymphocyte level was decreased more in group IIB than group IB. It was statistically significant. In microscopic findings, scores of SHI in normal group, group IB and IIB were 0.33, 4.47, and 1.96 each. Conclusions : Peucedani Radix might have inhibitory effect on lung fibrosis by reducing inflammatory cells in bleomycin-induced lung fibrosis model in mouse.

• Tuberculosis and Respiratory Diseases
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• 제67권5호
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• pp.436-444
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• 2009

Background: Micro computed tomography (CT) is rapidly developing as an imaging tool, especially for mice, which have become the experimental animal of choice for many pulmonary disease studies. We evaluated the usefulness of micro CT for evaluating lung fibrosis in the murine model of bleomycin-induced lung inflammation and fibrosis. Methods: The control mice (n=10) were treated with saline. The murine model of lung fibrosis (n=60) was established by administering bleomycin intra-tracheally. Among the 70 mice, only 20 mice had successful imaging analyses. We analyzed the micro CT and pathological findings and examined the correlation between imaging scoring in micro CT and histological scoring of pulmonary inflammation or fibrosis. Results: The control group showed normal findings on micro CT. The abnormal findings on micro CT performed at 3 weeks after the administration of bleomycin were ground-glass opacity (GGO) and consolidation. At 6 weeks after bleomycin administration, micro CT showed various patterns such as GGO, consolidation, bronchiectasis, small nodules, and reticular opacity. GGO (r=0.84) and consolidation (r=0.69) on micro CT were significantly correlated with histological scoring that reflected pulmonary inflammation (p<0.05). In addition, bronchiectasis (r=0.63) and reticular opacity (r=0.83) on micro CT shown at 6 weeks after bleomycin administration correlated with histological scoring that reflected lung fibrosis (p<0.05). Conclusion: These results suggest that micro CT findings from a murine model of bleomycin-induced lung fibrosis reflect pathologic findings, and micro CT may be useful for predicting bleomycin-induced lung inflammation and fibrosis in mice.

• Toxicological Research
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• 제26권2호
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• pp.137-147
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• 2010

Pulmonary fibrosis is a common consequence of many lung diseases and a leading cause of morbidity and mortality. The molecular mechanisms underlying the development of pulmonary fibrosis remain poorly understood. One model used successfully to study pulmonary fibrosis over the past few decades is the bleomycin-induced pulmonary fibrosis model. We aimed to identify the genes associated with fibrogenesis using an Affymetrix GeneChip system in a bleomycin-induced rat model for pulmonary fibrosis. To confirm fibrosis development, several analyses were performed, including cellular evaluations using bronchoalveolar lavage fluid, measurement of lactate dehydrogenase activity, and histopathological examinations. Common aspects of pulmonary fibrosis such as prolonged inflammation, immune cell infiltration, emergence of fibroblasts, and deposition of extracellular matrix and connective tissue elements were observed. Global gene expression analysis revealed significantly altered expression of genes ($\geq$ 1.5-fold, p < 0.05.) in a time-dependent manner during the development of pulmonary fibrosis. Our results are consistent with previous results of well-documented gene expression. Interestingly, the expression of triggering receptor expressed on myeloid cells 2 (Trem2), secreted phosphoprotein 1 (Spp1), and several proteases such as Tpsab1, Mcpt1, and Cma1 was considerably induced in the lung after bleomycin treatment, despite little evidence that they are involved in pulmonary fibrogenesis. These data will aid in our understanding of fibrogenic mechanisms and contribute to the identification of candidate biomarkers of fibrotic disease development.

• Tuberculosis and Respiratory Diseases
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• 제79권4호
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• pp.257-266
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• 2016

Background: Idiopathic pulmonary fibrosis is a common interstitial lung disease; it is a chronic, progressive, and fatal lung disease of unknown etiology. Over the last two decades, knowledge about the underlying mechanisms of pulmonary fibrosis has improved markedly and facilitated the identification of potential targets for novel therapies. However, despite the large number of antifibrotic drugs being described in experimental pre-clinical studies, the translation of these findings into clinical practices has not been accomplished yet. NADH:quinone oxidoreductase 1 (NQO1) is a homodimeric enzyme that catalyzes the oxidation of NADH to $NAD^+$ by various quinones and thereby elevates the intracellular $NAD^+$ levels. In this study, we examined the effect of increase in cellular $NAD^+$ levels on bleomycin-induced lung fibrosis in mice. Methods: C57BL/6 mice were treated with intratracheal instillation of bleomycin. The mice were orally administered with ${\beta}$-lapachone from 3 days before exposure to bleomycin to 1-3 weeks after exposure to bleomycin. Bronchoalveolar lavage fluid (BALF) was collected for analyzing the infiltration of immune cells. In vitro, A549 cells were treated with transforming growth factor ${\beta}1$ (TGF-${\beta}1$) and ${\beta}$-lapachone to analyze the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT). Results: ${\beta}$-Lapachone strongly attenuated bleomycin-induced lung inflammation and fibrosis, characterized by histological staining, infiltrated immune cells in BALF, inflammatory cytokines, fibrotic score, and TGF-${\beta}1$, ${\alpha}$-smooth muscle actin accumulation. In addition, ${\beta}$-lapachone showed a protective role in TGF-${\beta}1$-induced ECM expression and EMT in A549 cells. Conclusion: Our results suggest that ${\beta}$-lapachone can protect against bleomycin-induced lung inflammation and fibrosis in mice and TGF-${\beta}1$-induced EMT in vitro, by elevating the $NAD^+$/NADH ratio through NQO1 activation.