Mechanism of Yifei Decoction Combined with MitoQ on Inhibition of TGFß1/NOX4 and PDGF/ROCK Signal Pathway in Idiopathic Pulmonary Fibrosis.

ABSTRACT

BACKGROUND: Rho-related coiled helix forming protein kinase (Rho-ROCK) and another important fibrogenic factor-PDGF play a critical role in collagen deposition in rat lung tissue. Yifei decoction (YFT), a Chinese herbal decoction, has been used to treat idiopathic pulmonary fibrosis (IPF) in clinical practice and has produced positive outcomes; however, convincing evidence is currently lacking. The present study aimed to investigate the effects of YFT combined with MitoQ in rats with IPF and to explore the underlying mechanism. METHODS: Rat IPF model was established by endotracheal injection of 5 mg/kg BleomycinA5 into the specific pathogen-free SD rats. MitoQ (6.5 µmol/kg once daily), YFT (10 ml/kg once daily), and MitoQ + YFT (6.5 µmol/kg + 10 ml/kg once daily) were used to treat the rat model for 4 weeks, respectively. The normal rats without IPF were used as the controls. After 4 weeks of drug treatment, lung histopathology was assessed. Immunohistochemistry was used to detect the expression of fibronectin and collagen IV in lung tissue. The expression of IL-6, IL-1ß, TNF-α, GSH-Px, SOD, MDA, and hydroxyproline was determined by enzyme-linked immunosorbent assay. The expressions of TGFß1, NOX4, PDGFR-ß, and ROCK1 were determined using real-time quantitative PCR and Western blot. RESULTS: After 4 weeks of drug treatment, comparison of the MitoQ + YFT group with the IPF group showed that lung injury scores, W/D, lung tissue hydroxyproline, fibronectin, collagen IV content, and IL-6, IL-1ß, TNF-α, and MDA levels were significantly lower (P < 0.05), as well as the expression of TGFß1, NOX4, PDGFR-ß, and ROCK1, but the activity of GSH-Px and SOD was higher (P < 0.05). CONCLUSION: MitoQ combined with YFT can improve lung injury in rats with pulmonary fibrosis by reducing the secretion of proinflammatory cytokines and inhibiting TGFß1/NOX4 and PDGF/ROCK signaling pathways. It may provide a new method for the treatment of pulmonary fibrosis.