Hecker Matthias, Rose Matthias, Hecker Andreas, Dietrich Hartmut, Schaefer Martina B, Sommer Natascha, Seeger Werner, Mayer Konstantin
University of Giessen and Marburg Lung Center (UGMLC), University Hospital of Giessen, Justus-Liebig-University of Giessen, 35392 Giessen, Germany.
Department of General and Thoracic Surgery, University Hospital of Giessen, Justus-Liebig-University of Giessen, 35392 Giessen, Germany.
J Clin Med. 2020 Jun 29;9(7):2048. doi: 10.3390/jcm9072048.
Acute respiratory distress syndrome (ARDS) is associated with both high morbidity and mortality in intensive care units worldwide. Patients with ARDS often require parenteral nutrition with lipid emulsions as essential components. In the present study, we assessed the immunomodulatory and apoptotic effects of a modern, n-6-reduced lipid emulsion mixture in murine ARDS.
Mice received an infusion of either normal saline solution, pure long-chain triglyceride (LCT) emulsion, or SMOF (soybean oil, medium-chain triglycerides, olive oil, and fish oil) before a lipopolysaccharide (LPS) challenge. Mice were sacrificed at different time points (0, 24, or 72 h) after ARDS induction, and an analysis of inflammatory cytokines, protein concentrations, and the cellular composition of the alveolar and interstitial compartments was performed with special focus on alveolar apoptosis and necrosis.
Mice infused with SMOF showed decreased leukocyte invasion, protein leakage, myeloperoxidase activity, and cytokine production in alveolar spaces after LPS challenge compared to animals that received LCT. There were fewer cells in the lung interstitium of the SMOF group compared to the LCT group. Both lipid emulsions exerted pro-apoptotic and pro-necrotic properties on alveolar immune cells, with significantly increased necrosis in mice infused with LCT compared to SMOF.
SMOF has both anti-inflammatory and pro-resolving influences in murine ARDS. Partial replacement of n-6 fatty acids with n-3/n-9 fatty acids may therefore benefit critically ill patients at risk for ARDS who require parenteral nutrition.
急性呼吸窘迫综合征（ARDS）在全球重症监护病房中与高发病率和高死亡率相关。ARDS患者通常需要以脂质乳剂作为必需成分进行肠外营养。在本研究中，我们评估了一种现代的、n-6含量降低的脂质乳剂混合物对小鼠ARDS的免疫调节和凋亡作用。
在脂多糖（LPS）攻击前，小鼠接受生理盐水溶液、纯长链甘油三酯（LCT）乳剂或SMOF（大豆油、中链甘油三酯、橄榄油和鱼油）输注。在ARDS诱导后的不同时间点（0、24或72小时）处死小鼠，并对炎性细胞因子、蛋白质浓度以及肺泡和间质区室的细胞组成进行分析，特别关注肺泡凋亡和坏死情况。
与接受LCT的动物相比，输注SMOF的小鼠在LPS攻击后肺泡空间中的白细胞浸润、蛋白质渗漏、髓过氧化物酶活性和细胞因子产生均减少。与LCT组相比，SMOF组肺间质中的细胞较少。两种脂质乳剂均对肺泡免疫细胞发挥促凋亡和促坏死作用，与SMOF相比，输注LCT的小鼠坏死明显增加。
SMOF在小鼠ARDS中具有抗炎和促进恢复的作用。因此，用n-3/n-9脂肪酸部分替代n-6脂肪酸可能对有ARDS风险且需要肠外营养的危重症患者有益。
