马慢性阻塞性肺疾病的发病机制

N.E. Robinson, F.J. Derksen, M.A. Olszewski, V.A. Buechner-Maxwell
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引用次数: 232

摘要

目前的证据表明,马的慢性阻塞性肺病(COPD)是对吸入抗原,特别是生长在潮湿干草中的嗜热霉菌和放线菌的延迟超敏反应。在将易患copd的马暴露于这些干草的几个小时内,中性粒细胞侵入肺部并积聚在气道的管腔中,特别是细支气管。炎症反应伴随着支气管肺泡灌洗液中组胺水平升高,血浆中炎症介质血栓素和15-羟基二碳四烯酸(15-HETE)水平升高,气道黏膜分泌前列腺素(PG) E2减少。在慢性阻塞性肺病急性加重期间,气道表现出非特异性高反应性,并由于支气管痉挛和粘液和渗出物的积累而阻塞。支气管痉挛主要是由于乙酰胆碱(ACh)激活平滑肌毒蕈碱受体。由于体外平滑肌对乙酰胆碱的反应没有改变,气道平滑肌张力的增加可能是炎症介质激活气道反射的结果,而肺内非肾上腺素能非胆碱能神经系统和PGE2的产生等抑制机制的减少。弥漫性气道阻塞导致通气分布不均匀,通气/灌注不匹配,低氧血症。由于低氧血症和气道阻塞引起的呼吸驱动增加,马采用一种特有的呼吸策略,即在呼气开始时非常高的峰值流量随着呼气的进行而迅速减少。
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The pathogenesis of chronic obstructivepulmonary disease of horses

Present evidence suggests that chronic obstructive pulmonary disease (COPD) of horses is a delayed hypersensitivity response to inhaled antigens, particularly the thermophilic moulds and actinomycetes that grow in damp hay. Within several hours of exposing COPD-susceptible horses to such hay, neutrophils invade the lung and accumulate in the lumens of airways, particularly bronchioles. The inflammatory response is accompanied by increased levels of histamine in bronchoalveolar lavage fluid, increased plasma levels of the inflammatory mediators thromboxane and 15-hydroxyeicosatetraenoic acid (15-HETE), and a decrease in the production of prostaglandin (PG) E2 by the airway mucosa. During acute exacerbations of COPD, airways exhibit nonspecific hyperresponsiveness and become obstructed as a result of bronchospasm and the accumulation of mucus and exudates. Bronchospasm is due largely to activation of smooth muscle muscarinic receptors by acetylcholine (ACh). Because the in vitro response of smooth muscle to ACh is unaltered, the increase in airway smooth muscle tone is probably a result of activation of airway reflexes by inflammatory mediators and decreases in inhibitory mechanisms such as the intrapulmonary nonadrenergic noncholinergic nervous system and the production of PGE2 in affected horses. The diffuse airway obstruction leads to uneven distribution of ventilation, ventilation/ perfusion mismatching, and hypoxaemia. As a result of the increased respiratory drive caused by hypoxaemia and the presence of airway obstruction, horses adopt a characteristic breathing strategy in which very high peak flows at the start of exhalation rapidly diminish as exhalation proceeds.

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