Mayer Konstantin, Kiessling Almuth, Ott Juliane, Schaefer Martina Barbara, Hecker Matthias, Henneke Ingrid, Schulz Richard, Günther Andreas, Wang Jingdong, Wu Lijun, Roth Joachim, Seeger Werner, Kang Jing X
University of Giessen Lung Center (UGLC), Medical Clinic II, Justus-Liebig-University Giessen, Klinikstr. 36, D-35392 Giessen, Germany.
Am J Respir Crit Care Med. 2009 Mar 15;179(6):474-83. doi: 10.1164/rccm.200807-1064OC. Epub 2009 Jan 8.
Acute lung injury (ALI) remains an important cause of mortality in intensive care units. Inflammation is controlled by cytokines and eicosanoids derived from the n-6 fatty acid (FA) arachidonic acid (AA). The n-3 FA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and mediators derived from EPA and DHA possess reduced inflammatory potency.
To determine whether the ability of fat-1 mice to endogenously convert n-6 to n-3 FA, and thus generate an increased ratio of n-3 to n-6 FA, impacts experimental ALI.
We investigated ALI induced by intratracheal instillation of endotoxin in fat-1 and wild-type (WT) mice, assessing leukocyte numbers, protein concentration, and prostaglandin and cytokine levels in bronchoalveolar lavage fluid, as well as free FA in plasma, and lung ventilator compliance. Body temperature and motor activity of mice--markers of sickness behavior--were also recorded.
In ALI, fat-1 mice exhibited significantly reduced leukocyte invasion, protein leakage, and macrophage inflammatory protein-2 and thromboxane B(2) levels in lavage fluid compared with WT mice. Free AA levels were increased in the plasma of WT mice in response to endotoxin, whereas EPA and DHA were increased in the fat-1 group. Ventilator compliance was significantly improved in fat-1 mice. Body temperature and motor activity were decreased in ALI. fat-1 Mice recovered body temperature and motor activity faster.
fat-1 Mice exhibited reduced features of ALI and sickness behavior. Increasing the availability of n-3 FA may thus be beneficial in critically ill patients with ALI.
急性肺损伤（ALI）仍然是重症监护病房患者死亡的重要原因。炎症由源自n-6脂肪酸（FA）花生四烯酸（AA）的细胞因子和类花生酸控制。n-3脂肪酸二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）以及源自EPA和DHA的介质具有较低的炎症活性。
确定fat-1小鼠内源性将n-6转化为n-3脂肪酸从而使n-3与n-6脂肪酸比例增加的能力是否会影响实验性ALI。
我们研究了经气管内注入内毒素诱导的fat-1和野生型（WT）小鼠的ALI，评估支气管肺泡灌洗液中的白细胞数量、蛋白质浓度、前列腺素和细胞因子水平，以及血浆中的游离脂肪酸和肺通气顺应性。还记录了小鼠的体温和运动活动——疾病行为的指标。
在ALI中，与WT小鼠相比，fat-1小鼠灌洗液中的白细胞浸润、蛋白质渗漏以及巨噬细胞炎性蛋白-2和血栓素B2水平显著降低。WT小鼠血浆中游离AA水平因内毒素而升高，而fat-1组中EPA和DHA升高。fat-1小鼠的通气顺应性显著改善。ALI时体温和运动活动降低。fat-1小鼠恢复体温和运动活动更快。
fat-1小鼠ALI和疾病行为特征减轻。因此，增加n-3脂肪酸的可利用性可能对患有ALI的重症患者有益。
