Age influences inflammatory responses, hemodynamics, and cardiac proteasome activation during acute lung injury.
Age influences inflammatory responses, hemodynamics, and cardiac proteasome activation during acute lung injury.
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DOI：
10.3109/01902148.2014.999174
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发表时间：
2015-05
影响因子：
1.7
通讯作者：
Miller EJ
中科院分区：
文献类型：
--
作者：
Linge HM;Lee JY;Ochani K;Koga K;Kohn N;Ojamaa K;Powell SR;Miller EJ
急性肺损伤（acute lung injury，ALI）是危重病患者发病率和死亡率的重要来源。年龄是ALI临床结局的主要决定因素。老年人群中ALI相关死亡率的增加表明，对肺激发的反应存在年龄依赖性改变。这项观察性研究的目的是评价心脏和肺对肺激发的急性（6小时内）免疫和生理反应的年龄依赖性差异，这些反应可能导致严重程度增加。用来自革兰氏阳性细菌的细胞壁组分（脂磷壁酸和肽聚糖）对雄性C57 B1/6小鼠（年幼：2-3个月，年老：18-20个月）进行气管内攻击。6小时后，评估了攻击的生化和生理后果。测定肺泡炎细胞和蛋白浸润、肺泡气和血液细胞因子、心功能和心肌蛋白酶体活性。在幼龄小鼠中，对肺激发有剂量依赖性反应，导致气道中性粒细胞计数、肺通透性以及支气管肺泡灌洗液和血浆中细胞因子浓度增加。然后选择中等剂量以比较幼龄和老龄动物的反应。相比之下，老年动物在激发后表现出空气中中性粒细胞蓄积增加，动脉血氧饱和度、体温、血浆细胞因子浓度降低，心肌蛋白酶体反应缺乏。全身反应的发生和生命功能的维持（包括体温控制、氧饱和度和心肌蛋白酶体激活）存在明显的年龄依赖性差异。我们相信，更好地了解这些年龄相关的后果，急性肺损伤可以导致更适当的治疗老年患者群体。
Acute lung injury (ALI) is a significant source of morbidity and mortality in critically ill patients. Age is a major determinant of clinical outcome in ALI. The increased ALI-associated mortality in the older population suggests that there are age-dependent alterations in the responses to pulmonary challenge. The objective of this observational study was to evaluate age-dependent differences in the acute (within 6hrs) immunological and physiological responses of the heart and lung, to pulmonary challenge, that could result in increased severity. Male C57Bl/6 mice (young: 2–3 months, old: 18–20 months) were challenged intratracheally with cell wall components from gram positive bacteria (lipoteichoic acid and peptidoglycan). After 6h, both biochemical and physiological consequences of the challenge were assessed. Alveolar infiltration of inflammatory cells and protein, airspace and blood cytokines, cardiac function and myocardial proteasome activity were determined. In young mice there was a dose dependent response to pulmonary challenge resulting in increased airspace neutrophil counts, lung permeability, and concentrations of cytokines in bronchoalveolar lavage fluid and plasma. A midrange dose was then selected to compare the responses in young and old animals. In comparison, the old animals displayed increased neutrophil accumulation in the airspaces, decreased arterial oxygen saturation, body temperatures, plasma cytokine concentrations, and a lack of myocardial proteasome response, following challenge. Age dependent differences in the onset of systemic response and in maintenance of vital functions, including temperature control, oxygen saturation and myocardial proteasome activation, are evident. We believe a better understanding of these age-related consequences of ALI can lead to more appropriate treatments in the elderly patient population.