Effects of Chronic Intermittent Hypoxia on Allergen-Induced Airway Inflammation in Rats
Effects of Chronic Intermittent Hypoxia on Allergen-Induced Airway Inflammation in Rats
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DOI：
10.1165/rcmb.2014-0213oc
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发表时间：
2015-02-01
影响因子：
6.4
通讯作者：
Teodorescu, Mihaela
中科院分区：
文献类型：
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作者：
Broytman, Oleg;Braun, Rudolf K.;Teodorescu, Mihaela
阻塞性睡眠呼吸暂停加重哮喘，但其机制尚不清楚。慢性间歇性缺氧是睡眠呼吸暂停的一个显著特征。在这项研究中，我们测试了慢性间歇性缺氧对大鼠过敏原诱导炎症的影响。四组（n = 9-11/组）卵清蛋白（OVA）致敏的褐-挪威大鼠，在每周进行OVA或载药刺激的同时，进行间歇性缺氧（10%氧气，30个周期/小时，10小时/天）或正常缺氧，持续30天。最后一次给药后2天，比较各组肺生理、支气管肺泡灌洗白细胞差异计数和组织学（小天狼星红染色检测胶原含量）。采用定量PCR法检测支气管肺泡灌洗细胞中基因表达。与常氧相比，慢性间歇缺氧可降低FEV0.1/FVC比值（P = 0.005）、呼气峰流量（P = 0.002）和平均呼气中流量（P = 0.004），且以中、大气道为主；降低基线嗜酸性粒细胞数目（P = 0.01），放大OVA对单核细胞数目的影响（相互作用P = 0.02）；近端气道胶原蛋白密度增高（P = 0.008），远端气道胶原蛋白密度降低（P = 0.004）；肺周围质性肺气肿改变；M2巨噬细胞标志物m -1表达增加，ova诱导的纤溶酶原激活物抑制剂-1表达增强。慢性间歇性缺氧会改变对过敏原的免疫反应，使其向以t - h -1为主的细胞表型转变，并伴有胶原沉积和基质降解，从而导致气流受限。这些发现强调了睡眠呼吸暂停可能加重已有哮喘患者的气道功能障碍。
Obstructive sleep apnea aggravates asthma, but its mechanisms are unknown. Chronic intermittent hypoxia is one hallmark feature of sleep apnea. In this study, we tested the effects of chronic intermittent hypoxia on allergen-induced inflammation in rats. Four groups (n = 9-11/group) of ovalbumin (OVA)-sensitized Brown-Norway rats underwent intermittent hypoxia (10% oxygen, 30 cycles/h, 10 h/d) or normoxia for 30 days concurrent with weekly OVA or vehicle challenges. Lung physiology, differential leukocyte counts from bronchoalveolar lavage, and histology (Picro Sirius Red staining for collagen content) were compared between groups 2 days after the last challenge. Gene expression in bronchoalveolar lavage cells was quantified by quantitative PCR. Compared with normoxia, chronic intermittent hypoxia reduced the FEV0.1/FVC ratio (P = 0.005), peak expiratory flow (P = 0.002), and mean midexpiratory flow (P = 0.004), predominantly in medium and large airways; decreased the baseline eosinophil number (P = 0.01) and amplified the effect of OVA on monocyte number (P = 0.02 for the interaction); in proximal airways, increased (P = 0.008), whereas in distal airways it decreased (P = 0.004), collagen density; induced qualitative emphysematous changes in lung periphery; and increased expression of the M2 macrophage marker YM-1 and augmented OVA-induced expression of plasminogen activator inhibitor-1. Chronic intermittent hypoxia alters immune response to allergen toward a more T-H-1-predominant cellular phenotype with collagen deposition and matrix degradation, leading to airflow limitation. These findings highlight the potential of sleep apnea to aggravate airway dysfunction in patients with preexistent asthma.