| Purpose:Chronic obstructive pulmonary disease (COPD) is a kind of complex disease, a lot of inflammation cells are involved of COPD, for example, macrophages, neutrophils, T lymphocytes and B lymphocytes, eosinophils and epithelial cell. Inflammation mediators play an important role in COPD, such as cytokines and ROSs.COPD is a common respiratory disease worldwide. It’s largely unknown about the reason and mechanism of COPD development. The interaction of genetic susceptibility with environmental factors (e.g. environmental pollution, smoking, age, airway inflammation etc.) may be the primary contributors to the development of COPD. Smoking may play as an inducement among the factors chiefly. There is no useful way to cure COPD up to now. Bronchodilators and corticosteroids are the main prescribed drugs. It may be available to stop smoking.Recent studies indicated that acupuncture could improve life quality of COPD patients. It was noted that acupuncture treatment on COPD model rats can improve the lung ventilation by orexin system in our laboratory. However, the anti-inflammation role of acupuncture in the complex development of COPD remains unknown. Previous research has shown that vagus nerve discharge was increase and cholinergic anti-inflammatory pathway was activated via selecting acupoint of Zusanli. Therefore, we speculated that acupuncture can decrease inflammatory response by activating vagus nerve discharge in a rat model of cigarette smoke-induced COPD. In this study, we want to investigate the mechanism of acupuncture and its effect on anti-inflammation.Part.1:The COPD model (cigarette smoke-exposed rats with12weeks) was evaluated on the basis of pulmonary function tests and lung pathology. Alveolar lavage fluid cytokines level and ROS level were measured and analyzed for the protection (anti-inflammation and antioxidant mechanism) of EA in COPD model.Part.2:The early COPD model (cigarette smoke-exposed rats with3weeks) was operated on surgical division of vagus nerve fibers unilaterally to observe the role of vagus nerve. Lung pathology and alveolar lavage fluid cytokines level and ROS level were detected also to analyze whether the effect of EA on COPD model through vagus nerve.Methods:1. The Sprague-Dawley rats were exposed to cigarette smoke in an incomplete airtight cage for1h/twice/day lasting for3weeks or12weeks. At the end of3or12weeks, the smoke-exposed rats were evaluated as to their suitability as an experimental model of COPD using measures of pulmonary function and lung pathology.2. Alveolar lavage fluid TNF-α and IL-1β levels were detected with ELISA method.3. Alveolar lavage fluid MDA level was detected;4. Electroacupuncture on COPD rats was performed for30min/day during2weeks via selecting acupoint of ZUSANLI.5. Unilateral vagotomy (left).6. Vagus nerve discharge was recorded during EA.Results:Part.1Effects of EA on COPD model1. The lung pathological changes were observed by haematoxylin and eosin-stained sections after12weeks in smoke-exposed rats. Photomicrographs showed coalesced lung alveolar and inflammnatory cells in the thickened bronchial wall of model rats. The average walls of bronchi and bronchiole were significantly thicker in smoke-exposed compared with control rats (P<0.01, P<0.001). Compared with control rats, pulmonary function in model rats had deteriorated with evidence of decreased dynamic compliance (P<0.01) and increased airway resistance (P<0.01). Alveolar lavage fluid TNF-α and IL-1β level increased (both P<0.001), alveolar lavage fluid MDA level increased (P<0.05) too in smoke-exposed compared with control rats.2. After EA treatment, The lung pathological changes showed that bronchi and bronchiole wall thickness decreased (P<0.05, P<0.01) in model rats compared without EA. Lung function had improved with the pulmonary dynamic compliance increase (P<0.05), and airway resistance decrease (P<0.05). Alveolar lavage fluid TNF-α and IL-1β level decreased (both P<0.05), but still higher than control rat (P<0.05), alveolar lavage fluid MDA level decreased (P<0.05).Part.2Effects of EA on early COPD model1. There are no obvious changes of lung dry/wet ratio, lung pathology and IL-1β level between in control rats with unilateral vagotomy or without unilateral vagotomy.2. At the end of3weeks, smoke-exposed rats were evaluated as early model of COPD. Pulmonary edema was obvious, lung dry/wet ratio was smaller (P<0.001), bronchiole wall was significantly thicker (P<0.001), alveolar lavage fluid IL-1β level was greater (P<0.01) in early COPD model rats compared with control rats. But no change was in MDA and TNF-a level.3. After unilateral vagotomy, there was no difference in lung dry/wet ratio and bronchiole wall thickness between early COPD and control rats. Alveolar lavage fluid IL-1β level increased (P<0.05) only.4. Lung dry/wet ratio increased (P<0.05), bronchiole wall thickness decreased (P<0.01) and alveolar lavage fluid IL-1β level was smaller (P<0.01) in early COPD rats with EA treatment compared without EA.5. There was no change in lung tissue dry/wet ratio and alveolar lavage fluid IL-lplevel, bronchiole wall thickness decreased (P<0.001) in early COPD by unilateral vagotomy and EA compared with early COPD rats.6. Vagus nerve discharge increased following EA treatments in early COPD compared without EA.Conclusions:1. Lung function decreased, bronchi and bronchiole wall thickness increased in smoke-exposed COPD model. The COPD model was established successfully because it fit the characteristics of the pathologic change and lung function in COPD patients.2. Alveolar lavage fluid TNF-a, IL-1β and MDA level increased in COPD model.3. Early COPD model was established successfully because it fit the characteristics of the pathologic change and lung tissue dry/wet ratio decreased and alveolar lavage fluid IL-1β level increased.4. EA treatment can improve lung function in COPD and early COPD models.5. EA effect on COPD model may be through vagus nerve. |
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