Abstract
The current study aims to investigate the effects of matrine on the JAK-STAT signaling transduction pathways in bleomycin (BLM)-induced pulmonary fibrosis (PF) and to explore its action mechanism. A total of 72 male C57BL/6 mice were randomized into the control, model, and treatment groups. PF models were established by instilling BLM intratracheally. The treatment group was given daily matrine through gastric lavage. Six mice were sacrificed in each group at 3, 7, 14, and 28 days. The lung tissues were observed using hematoxylin-eosin staining. The expression of JAK, STAT1, and STAT3 was observed using immunohistochemistry and then determined using real-time polymerase chain reaction. Alveolitis and PF significantly improved in the treatment group compared with the model group (P < 0.05). The expression of JAK, STAT1, and STAT3 in the model group increased at day 7, peaked at day 14 and then decreased, but the expression was still higher than that in the control group at day 28 (P < 0.05). The three indices in the treatment group were significantly lower than those in the model group at any detection time point (P < 0.05). PF causes high expression of JAK, STAT1, and STAT3. Matrine exerts an anti-PF effect by inhibiting the JAK-STAT signaling transduction pathways.
Highlights
Idiopathic pulmonary fibrosis (PF) is primarily manifested by interstitial cell hyperplasia and the excessive deposition of extracellular matrixes dominated by collagen proteins (Gross and Hunningghake, 2001)
Noticeable alveolitis occurred in the tissues, with exudative changes in the pulmonary alveoli at day 3; at day 7, exudation turned more serious and inflammatory cell infiltration appeared; from 14 day to 28 day, alveolitis and exudation eased gradually, fibrosis aggravated gradually with noticeably increased alveolar septa, most alveolar structures were destroyed and pulmonary alveoli varied in volume
PF is associated with Just another Kinases (JAKs)-Signal transducers and activators of transcription (STATs) signaling transduction pathways (Eitzman et al, 1996; Fan et al, 2003; Kim et al, 2002; Wang et al, 2009)
Summary
Idiopathic pulmonary fibrosis (PF) is primarily manifested by interstitial cell hyperplasia and the excessive deposition of extracellular matrixes dominated by collagen proteins (Gross and Hunningghake, 2001). Different JAK-STAT pathways are activated by different cytokines (Ratthe et al, 2007). Among these pathways, the activation of JAK-STAT3 is closely correlated with the occurrence of fibrotic diseases, inhibitors of this pathway are promising to become the target of new drugs developed for these diseases (Ahn et al, 2009; Tu et al, 2005). Lightyellow sophora root is the dried root of Sophora flavescens ait (leguminosae). Matrine is the major active component of the alkaloids of Sophora flavescens ait, and it has multiple pharmacologic actions and effects (Cao et al, 2010; Jiang et al, 2007; Liu et al, 2007; Yang et al, 2007). In the process of the initiation of PF, the mechanism of free radical injury plays a crucial role
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