Oxygenation inhibits the physiological tissue-protecting mechanism and thereby exacerbates acute inflammatory lung injury.
Oxygenation inhibits the physiological tissue-protecting mechanism and thereby exacerbates acute inflammatory lung injury.
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氧合抑制了生理组织保护机制，从而加剧了急性炎症肺损伤。
DOI：
10.1371/journal.pbio.0030174
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发表时间：
2005-06
期刊：
影响因子：
9.8
通讯作者：
Sitkovsky, MV
中科院分区：
文献类型：
--
作者：
Thiel, M;Chouker, A;Ohta, A;Jackson, E;Caldwell, C;Smith, P;Lukashev, D;Bittmann, I;Sitkovsky, MV
急性呼吸窘迫综合征（ARDS）通常需要通过插管和机械通气并补充使用高浓度氧气进行对症支持治疗。尽管氧疗是一种挽救生命的措施，但最近发现的一种关键的组织保护机制预测，对患有不受控制的肺部炎症的ARDS患者给予氧疗也可能具有危险的副作用。氧合可能削弱局部组织缺氧驱动和腺苷A2A受体（A2AR）介导的抗炎机制，从而进一步加重肺损伤。在这里，我们报告野生型和腺苷A2AR缺陷小鼠的实验，证实了预测的氧气的影响。这些结果还表明，由于氧合相关的A2AR介导的肺组织保护途径的消除，给氧后医源性急性肺损伤加重的可能性。我们表明，这种潜在的并发症，临床上广泛使用的氧合程序可以完全预防肺内注射的选择性A2AR激动剂，以弥补氧合相关的损失的肺组织保护内源性腺苷。在急性肺部炎症条件下氧疗的主要医源性并发症的确定引起了对需要氧疗的ARDS患者进行临床和流行病学研究的需要。建议对ARDS和其他肺部炎症原因患者的氧疗应与抗炎措施相结合，例如，吸入应用A2AR激动剂。报告的观察结果也可能回答长期存在的问题，即为什么肺最容易受到炎症损伤，以及为什么肺衰竭通常先于多器官衰竭。一个小鼠模型表明，氧疗可能通过削弱缺氧驱动的抗炎机制而加剧肺损伤。
Acute respiratory distress syndrome (ARDS) usually requires symptomatic supportive therapy by intubation and mechanical ventilation with the supplemental use of high oxygen concentrations. Although oxygen therapy represents a life-saving measure, the recent discovery of a critical tissue-protecting mechanism predicts that administration of oxygen to ARDS patients with uncontrolled pulmonary inflammation also may have dangerous side effects. Oxygenation may weaken the local tissue hypoxia-driven and adenosine A2A receptor (A2AR)-mediated anti-inflammatory mechanism and thereby further exacerbate lung injury. Here we report experiments with wild-type and adenosine A2AR-deficient mice that confirm the predicted effects of oxygen. These results also suggest the possibility of iatrogenic exacerbation of acute lung injury upon oxygen administration due to the oxygenation-associated elimination of A2AR-mediated lung tissue-protecting pathway. We show that this potential complication of clinically widely used oxygenation procedures could be completely prevented by intratracheal injection of a selective A2AR agonist to compensate for the oxygenation-related loss of the lung tissue-protecting endogenous adenosine. The identification of a major iatrogenic complication of oxygen therapy in conditions of acute lung inflammation attracts attention to the need for clinical and epidemiological studies of ARDS patients who require oxygen therapy. It is proposed that oxygen therapy in patients with ARDS and other causes of lung inflammation should be combined with anti-inflammatory measures, e.g., with inhalative application of A2AR agonists. The reported observations may also answer the long-standing question as to why the lungs are the most susceptible to inflammatory injury and why lung failure usually precedes multiple organ failure. A mouse model suggests that oxygen therapy may exacerbate lung injury by weakening the anti-inflammatory mechanisms driven by hypoxia.
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DOI：
10.1165/rcmb.2002-0004oc
发表时间：
2003-02-01
影响因子：
6.4
作者：
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通讯作者：
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影响因子：
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