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      Effect of Bufei Yishen Granules Combined with Electroacupuncture in Rats with Chronic Obstructive Pulmonary Disease via the Regulation of TLR-4/NF- κB Signaling

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          Abstract

          Background

          The combined therapy of Bufei Yishen granules (BY) and electroacupuncture (EA) has shown good effects clinically in treating chronic obstructive pulmonary disease (COPD). The present study aimed to observe the effects of the BY + EA combination in a COPD rat model and dissect the potential mechanisms via Toll-like receptor (TLR) 4/nuclear factor kappa B (NF- κB) signaling.

          Methods

          The COPD rats were treated with normal saline, aminophylline, Bufei Yishen granules, electroacupuncture, or Bufei Yishen granules combined with electroacupuncture. The pulmonary function; lung tissue histology; levels of inflammatory factors; expression levels of TLR-4, inhibitor of nuclear factor kappa B (I κB), and NF- κB; and activation of NF- κB in the lung tissues were evaluated.

          Results

          Pulmonary function was markedly decreased in the COPD rats, and the lung tissue histology of the COPD rats showed severe pathological changes. The pulmonary function and lung tissue morphology in the treatment groups (APL, BY, EA, and BY + EA) were improved. The increased levels of the inflammatory cytokines interleukin (IL)-1 β and IL-6 indicated a chronic inflammatory state in the COPD rats. In the BY, EA, and BY + EA groups, the levels of IL-1 β and IL-6 were decreased, especially in the BY + EA group. In addition, the mRNA and protein expression levels of TLR-4, I κB, and NF- κB were obviously downregulated in the BY and BY + EA groups; and the NF- κB p65 activation was significantly decreased in the BY, EA, and BY + EA groups.

          Conclusions

          Bufei Yishen granules and electroacupuncture have curative effects in COPD rats, and the combination therapy of Bufei Yishen granules and electroacupuncture is superior. The TLR-4/NF- κB pathway may be involved in the potential mechanisms by which Bufei Yishen granules and electroacupuncture reduce inflammation.

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          Most cited references46

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          Chronic obstructive pulmonary disease.

          Chronic obstructive pulmonary disease (COPD) is a common disease with high global morbidity and mortality. COPD is characterized by poorly reversible airway obstruction, which is confirmed by spirometry, and includes obstruction of the small airways (chronic obstructive bronchiolitis) and emphysema, which lead to air trapping and shortness of breath in response to physical exertion. The most common risk factor for the development of COPD is cigarette smoking, but other environmental factors, such as exposure to indoor air pollutants - especially in developing countries - might influence COPD risk. Not all smokers develop COPD and the reasons for disease susceptibility in these individuals have not been fully elucidated. Although the mechanisms underlying COPD remain poorly understood, the disease is associated with chronic inflammation that is usually corticosteroid resistant. In addition, COPD involves accelerated ageing of the lungs and an abnormal repair mechanism that might be driven by oxidative stress. Acute exacerbations, which are mainly triggered by viral or bacterial infections, are important as they are linked to a poor prognosis. The mainstay of the management of stable disease is the use of inhaled long-acting bronchodilators, whereas corticosteroids are beneficial primarily in patients who have coexisting features of asthma, such as eosinophilic inflammation and more reversibility of airway obstruction. Apart from smoking cessation, no treatments reduce disease progression. More research is needed to better understand disease mechanisms and to develop new treatments that reduce disease activity and progression.
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            Role of inflammatory cells in airway remodeling in COPD

            COPD is characterized by chronic bronchitis, chronic airway obstruction, and emphysema, leading to a progressive and irreversible decline in lung function. Inflammation is central for the development of COPD. Chronic inflammation in COPD mainly involves the infiltration of neutrophils, macrophages, lymphocytes, and other inflammatory cells into the small airways. The contribution of resident airway structural cells to the inflammatory process is also important in COPD. Airway remodeling consists of detrimental changes in structural tissues and cells including airway wall thickening, epithelial metaplasia, goblet cell hypertrophy, and smooth muscle hyperplasia. Persistent airway inflammation might contribute to airway remodeling and small airway obstruction. However, the underlying mechanisms remain unclear. In this review, we will provide an overview of recent insights into the role of major immunoinflammatory cells in COPD airway remodeling.
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              COPD immunopathology

              The immunopathology of chronic obstructive pulmonary disease (COPD) is based on the innate and adaptive inflammatory immune responses to the chronic inhalation of cigarette smoking. In the last quarter of the century, the analysis of specimens obtained from the lower airways of COPD patients compared with those from a control group of age-matched smokers with normal lung function has provided novel insights on the potential pathogenetic role of the different cells of the innate and acquired immune responses and their pro/anti-inflammatory mediators and intracellular signalling pathways, contributing to a better knowledge of the immunopathology of COPD both during its stable phase and during its exacerbations. This also has provided a scientific rationale for new drugs discovery and targeting to the lower airways. This review summarises and discusses the immunopathology of COPD patients, of different severity, compared with control smokers with normal lung function.
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                Author and article information

                Contributors
                Journal
                Evid Based Complement Alternat Med
                Evid Based Complement Alternat Med
                ECAM
                Evidence-based Complementary and Alternative Medicine : eCAM
                Hindawi
                1741-427X
                1741-4288
                2019
                29 May 2019
                29 May 2019
                : 2019
                : 6708645
                Affiliations
                1Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
                2Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment & Chinese Medicine Development of Henan Province, Henan University of Chinese Medicine, Zhengzhou, Henan 450046, China
                3Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, Henan 450046, China
                Author notes

                Academic Editor: Gerhard Litscher

                Author information
                http://orcid.org/0000-0002-5849-4504
                http://orcid.org/0000-0002-2714-9353
                Article
                10.1155/2019/6708645
                6560336
                31275415
                6be4684d-478f-46a9-ba76-00750f8f8c6d
                Copyright © 2019 Jindi Ma et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 3 December 2018
                : 29 April 2019
                : 15 May 2019
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81673942
                Award ID: 81603473
                Funded by: Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment
                Funded by: Chinese Medicine Development of Henan Province
                Categories
                Research Article

                Complementary & Alternative medicine
                Complementary & Alternative medicine

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