Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Adv Exp Med Biol. 2010;662:27-32. doi: 10.1007/978-1-4419-1241-1_3.
Reduction of alveolar PO(2) (alveolar hypoxia, AH) may occur in pulmonary diseases such as chronic obstructive pulmonary disease (COPD), or in healthy individuals ascending to altitude. Altitude illnesses may develop in non-acclimatized persons who ascend rapidly. The mechanisms underlying these illnesses are not well understood, and systemic inflammation has been suggested as a possible contributor. Similarly, there is evidence of systemic inflammation in the systemic alterations present in COPD patients, although its role as a causative factor is not clear.We have observed that AH, induced by breathing 10% O(2) produces a rapid (minutes) and widespread micro vascular inflammation in rats and mice. This inflammation has been observed directly in the mesenteric, skeletal muscle, and pial microcirculations. The inflammation is characterized by mast cell degranulation, generation of reactive O(2) species, reduced nitric oxide levels, increased leukocyte-endothelial adherence in post-capillary venules, and extravasation of albumin. Activated mast cells stimulate the renin-angiotensin system (RAS) which leads to the inflammatory response via activation of NADPH oxidase. If the animals remain in hypoxia for several days, the inflammation resolves and exposure to lower PO(2) does not elicit further inflammation, suggesting that the vascular endothelium has "acclimatized" to hypoxia.Recent experiments in cremaster microcirculation suggest that the initial trigger of the inflammation is not the reduced tissue PO(2), but rather an intermediary released by alveolar macrophages into the circulation. The putative intermediary activates mast cells, which, in turn, stimulate the local renin-angiotensin system and induce inflammation.
肺泡 PO(2) 的降低（肺泡缺氧，AH）可能发生在肺部疾病中，如慢性阻塞性肺疾病（COPD），或在健康个体上升到高海拔地区时。在没有适应的人快速上升时，可能会发生高原病。这些疾病的机制尚未得到很好的理解，全身性炎症被认为是一个可能的原因。同样，在 COPD 患者存在的系统性改变中也有证据表明存在系统性炎症，尽管其作为致病因素的作用尚不清楚。我们已经观察到，呼吸 10%O(2) 引起的 AH 在大鼠和小鼠中迅速（数分钟）产生广泛的微血管炎症。这种炎症已经在肠系膜、骨骼肌和软脑膜微循环中直接观察到。炎症的特征是肥大细胞脱颗粒、活性氧（O2）物种的产生、一氧化氮水平降低、后毛细血管静脉中的白细胞-内皮细胞黏附增加以及白蛋白外渗。活化的肥大细胞刺激肾素-血管紧张素系统（RAS），通过激活 NADPH 氧化酶引发炎症反应。如果动物在缺氧状态下持续数天，炎症就会消退，而暴露于较低的 PO(2) 不会引起进一步的炎症，这表明血管内皮已经对缺氧“适应”。最近在精索微循环中的实验表明，炎症的初始触发因素不是组织 PO(2) 的降低，而是肺泡巨噬细胞释放到循环中的中间产物。推测的中间产物激活肥大细胞，反过来又刺激局部肾素-血管紧张素系统并引发炎症。
