Long-term effects of three Tiao-Bu Fei-Shen therapies on NF-κB/TGF-β1/smad2 signaling in rats with chronic obstructive pulmonary disease

Abstract

BackgroundThe three Tiao-Bu Fei-Shen (Bufei Jianpi, Bufei Yishen, Yiqi Zishen) granules have been confirmed for their beneficial clinical efficacy in chronic obstructive pulmonary disease (COPD) patients on reducing frequency and duration of acute exacerbation, improving syndromes, pulmonary function and exercise capacity. But the short- or long-term mechanism of them is not fully clear. Nuclear factor (NF)-κB/transforming growth factor (TGF)-β1/smad2 signaling pathway is involved in the progress of inflammation and remodeling in chronic obstructive pulmonary disease COPD. This study aimed to explore the long-term effects mechanism of Tiao-Bu Fei-Shen granules by regulating NF-κB/TGF-β/Smads signaling in rats with COPD.MethodsSprague Dawley rats were randomized into control, model, Bufei Jianpi, Bufei Yishen, Yiqi Zishen and aminophylline groups. COPD rats, induced by cigarette smoke and bacterial infections exposures, were administrated intragastricly by normal saline, Bufei Jianpi, Bufei Yishen, Yiqi Zishen granules or aminophylline from week 9 through 20, respectively. At week 20 and 32, lung tissues were harvested. Immunohistochemistry was used to detect interleukin (IL)-1β and tumor necrosis factor (TNF)-α, quantitative real-time polymerase chain reaction (qRT-PCR) was used for TGF-β1 and Smad2 mRNA analysis, western blotting was used to determine the phosphorylation of NF-κB (p-NF-κB) and IκBα (p-IκBα).ResultsCOPD rats had marked airway injury, such as chronic airway inflammation and remodeling, emphysema, which were improved in the three traditional Chinese medicines (TCM)-treated animals. The levels of IL-1β, TNF-α, p-NF-κB, p-IκBα, TGF-β1 and Smad2 were significantly higher in COPD rats than in controls, while they were dramatically reduced in the three TCM- and aminophylline-treated groups. At the meantime, all these endpoints were significantly lower in three TCM-treated groups than in aminophylline group, especially in Bufei Jianpi and Bufei Yishen groups. Compared to week 20, all endpoints decreased significantly in three TCM groups at week 32.ConclusionThe three Tiao-Bu Fei-Shen therapies can reduce pulmonary inflammation and remodeling in COPD and have significant long-term effects. NF-κB/TGF-β1/smad2 signaling might be involved in the mechanism.

Exercise-modulated epigenetic markers and inflammatory response in COPD individuals: A pilot study

“…According to the data, our study is the first to demonstrate reduction on systemic TGF-β levels after acute exercise in trained COPD patients. Previously, Li et al (2014) showed that COPD rats, induced by cigarette smoke and bacterial infections exposures, reduced their TGF-β levels after 32 weeks of traditional Chinese medicine. Thus, decreasing TGF-β after 24 exercise sessions may suggest a better inflammatory control on COPD.…”

Role of bone marrow mesenchymal stem cells in the development of PQ‑induced pulmonary fibrosis

“…Reduced pulmonary inflam-(�8,�9). Reduced pulmonary inflammation may therefore contribute to the recovery from lung injury (40,41).…”

Dynamic Characteristics of Sequential Acute Exacerbations and Risk Windows in AECOPD Rats Induced by Cigarette-Smoke and Exposure to <i>Klebsiella pneumoniae</i>

“…25) To mimic an AE, orotracheal intubation injections containing KP (6×10 14 CFU per mL, 0.1 mL) were used to challenge the rats after they were anesthetized using 10% chloral hydrate at a dose of 2.8 mL/kg body weight. 19,26,27) In the AE1 group, the challenges were performed on Days 1 and 15, which were counted from the first day of week 9; and in the AE2 group, the challenges were performed on Days 1 and 23.…”

“…16,17) Klebsiella pneumoniae, which is one of top three pathogens causing COPD deterioration 18) and has been used to prepare animal models of COPD at the stable stage and the acute exacerbation stage. 19,20) In this study, we used rat model of COPD and AECOPD that induces significantly lower pulmonary function, especially in acute inflammatory reactions, 19,[21][22][23][24][25][26][27] to explore dynamic inflammatory features during and after an acute bacterial challenge with Klebsiella pneumoniae in a COPD rat model. The rats were challenged with an additional exacerbation at a different time-point to determine variations in the temporal course of AE and the subsequent RW.…”