Mechanism of Yifei Decoction Combined with MitoQ on Inhibition of TGFβ1/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-1β, TNF-α, GSH-Px, SOD, MDA, and hydroxyproline was determined by enzyme-linked immunosorbent assay. The expressions of TGFβ1, NOX4, PDGFR-β, 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-1β, TNF-α, and MDA levels were significantly lower (P < 0.05), as well as the expression of TGFβ1, NOX4, PDGFR-β, 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 TGFβ1/NOX4 and PDGF/ROCK signaling pathways. It may provide a new method for the treatment of pulmonary fibrosis.