Abstract
Objective The aim of the current study was to investigate the protective effect of Yangyin Yiqi Mixture (YYYQ) on Bleomycin-induced pulmonary fibrosis in rats based on TGF-β1/Smad signal pathway and epithelial to mesenchymal transition (EMT). Methods 120 Wistar rats were randomly divided into six groups: control group, BLM group, BLM + Pred group, BLM+YYYQ-L group, BLM+YYYQ-M group, and BLM+YYYQ-H group. Rats were given an intratracheal instillation of 3 mg/kg BLM to establish the pulmonary fibrosis model and followed by different dosages of YYYQ (11, 22, 44g/kg, via intragastric gavage) or prednisone soluble (4.2mg/kg, via intragastric gavage) or water. After 14 days and 28 days, tissue sections were stained with hematoxylin-eosin and Masson's trichrome to observe histopathological changes. Protein levels of TGF-β1, CTGF, Interleukin 18, and hydroxyproline were detected by ELISA method, and mRNA expressions of TGF-β1, TβRI, TβRII, Smad3, Smad7, α-SMA, E-cadherin, laminin, and collagen I were detected by RT-PCR. Results TGF-β1, CTGF, Interleukin 18, and hydroxyproline levels and mRNA expression of TGF-β1, TβRI, TβRII, Smad3, α-SMA, laminin, and collagen I were significantly increased (p <0.01), while Smad7 and E-cadherin levels were significantly decreased in BLM group (p <0.01). YYYQ-M and YYYQ-H group had downregulated the TGF-β1, CTGF, hydroxyproline contents, and mRNA expression of TGF-β1, TβRI, TβRII, Smad3, α-SMA, laminin, and collagen I and upregulated mRNA levels of Smad7 and E-cadherin significantly (p <0.01 or p <0.05). The result from the present study, which was also supported by histological evidence, suggested that YYYQ-M group and YYYQ-H group exhibited better treatment effect on Bleomycin-induced pulmonary fibrotic rats when compared to that of BLM + Pred group (p <0.01). Meanwhile, the effect of YYYQ, in three different dosages, on the level of interleukin 18 was not significant. Conclusion These results showed that YYYQ has the potential of ameliorating the progression of pulmonary fibrosis, and the mechanism may be related to suppressing TGF-β1/Smad signal pathway and EMT in BLM-induced pulmonary fibrosis of rats.
Highlights
Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease, which is characterized by chronic inflammatory response, excessive proliferation of fibroblasts, aberrant deposition of extracellular matrix (EMC), and abnormal repair and remodeling of lung tissue [1]
Protein levels of Transforming growth factor-β1 (TGF-β1), Connective tissue growth factor (CTGF), Interleukin 18, and hydroxyproline were detected by Enzyme-Linked Immunosorbent Assay (ELISA) method, and mRNA expressions of TGF-β1, TβRI, Transforming growth factor-β1 receptor II CTGF (TβRII), Smad3, Smad7, α-Smooth muscle actin standard deviation (SD) (α-SMA), E-cadherin, laminin, and collagen I were detected by Real-Time Polymerase Chain Reaction (RT-PCR)
These results showed that Yangyin Yiqi Mixture IPF (YYYQ) has the potential of ameliorating the progression of pulmonary fibrosis, and the mechanism may be related to suppressing TGF-β1/Smad signal pathway and epithelial to mesenchymal transition (EMT) in BLM-induced pulmonary fibrosis of rats
Summary
Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease, which is characterized by chronic inflammatory response, excessive proliferation of fibroblasts, aberrant deposition of extracellular matrix (EMC), and abnormal repair and remodeling of lung tissue [1]. Since IPF can deteriorate lung functions, which may lead to respiratory failure and eventually death, the prognosis of IPF is usually. Studies had reported that combination of glucocorticosteroids (such as prednisone), azathioprine, and N-acetylcysteine was unable to decrease the mortality and morbidity rate of IPF, such combination remained as the conventional treatment for IPF patients in order to relieve inflammation, suppress immune responses, and relieve signs and symptoms during the course of the disease [6]. Pirfenidone and nintedanib are the two newly developed antipulmonary fibrotic drugs which can significantly improve lung function and delay the progression of IPF.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Evidence-Based Complementary and Alternative Medicine
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
