慢性间歇性缺氧对哮喘小鼠模型糖皮质激素敏感性的影响及机制探讨

Evidence is mounting that obstructive sleep apnea hypopnea syndrome (OSAHS) can aggravate the condition of bronchial asthma and is a risk factor for acute exacerbations. Its treatment with continuous positive airway pressure (CPAP) improves asthma outcomes .But the mechanisms are not clear. Chronic intermittent hypoxia（CIH） is the typical characteristic of OSAHS, which is the important pathological basis of its complications. Our previous studies suggested that CIH can lead to oxidative stress and airway inflammation in the asthma mouse model. In addition, oxidative stress can increase the activity of p38 MAPK, while p38 MAPK is involved in airway inflammation and remodeling, and plays an important role in the development of asthma resistance. Our hypothesis is that CIH can lead to production of oxidative stress and activation of p38 MAPK signaling pathway, leading to decreased glucocorticoid sensitivity. In this study, we try to establish mouse models by CIH combined with ovalbumin to explore effect of CIH on glucocorticoid sensitivity in asthmatic models and the possible mechanism implied, in order to explore a potential new therapeutic approch for asthma patients with OSAHS.

越来越多的证据显示阻塞性睡眠呼吸暂停低通气综合征会加重哮喘的病情，并且是其急性发作的危险因素，而持续气道正压治疗则可以改善哮喘治疗效果，但其中的机制尚不明确。慢性间歇性缺氧是阻塞性睡眠呼吸暂停低通气综合征的典型特征，是其并发症产生的重要病理基础。我们的前期研究发现：在哮喘小鼠模型中，慢性间歇性缺氧可以导致氧化应激状态的产生及气道炎症增加；氧化应激可以增加p38 MAPK活性，而p38 MAPK参与气道炎症、气道高反应性与重塑，在哮喘激素抵抗的发生中具有重要意义。我们的假设是慢性间歇性缺氧可以产生氧化应激状态，激活p38 MAPK信号通路，继而导致糖皮质激素敏感性下降。本研究拟通过慢性间歇性缺氧联合卵蛋白雾化建立小鼠模型，探讨慢性间歇性缺氧对哮喘小鼠糖皮质激素敏感性的影响及机制，为改善哮喘合并OSAHS患者糖皮质激素敏感性提供新的治疗思路。