BACKGROUND Critically ill patients are at higher risk having acute lung injury (ALI) and more often in need of parenteral nutrition. We sought to study whether preconditioning with representative of lipid emulsions for one week could benefit rats from ALI. METHODS Using a lipopolysaccharide (LPS)-induced ALI rat model and techniques such as polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. RESULTS PGE2 production in the serum was highest in the LPS group, followed with Intralipid group, and the PGE2 level of these two groups was significantly (P < 0.05) higher than the rest. Intralipid conditioning caused significantly less production of LTB4 than the LPS, Clinoleic, or Omegaven group. In contrast to Intralipid, rats pretreated with Clinoleic or Omegaven significantly decreased their production of inflammatory mediators (IL-1 β, IL-6 and TNF-α), had less apoptosis in the lung tissues, and Omegaven greatly improved liver function upon lipopolysaccharide (LPS) challenge. CONCLUSIONS In an ALI setting, preconditioning with Omegaven or Clinoleic was better than Intralipid in decreasing the intensity of the cytokine storm and apoptosis caused by LPS challenge, and Omegaven in addition had the potential to improve liver function. The results from the present study set a basis for further investigation of the molecular mechanisms of ALI, including the up- and downstream pathways of proinflammatory factor production, in search of (small) molecules intervening with the pathogenesis of ALI in order to translate relevant research findings into clinical benefit for patients with ALI. The use of Omegaven or Clinoleic, particularly in patients with ALI, is still characterized by uncertainty due to a lack of relevant studies. Future investigations must specifically focus on the route of administration and mode of application (enteral vs. parenteral/bolus vs. continuous), determining an optimal dose of Omegaven or Clinoleic, and the defining the best timepoint(s) for administration. Critically ill patients are at higher risk having acute lung injury (ALI) and more often in need of parenteral nutrition. The effect of lipid emulsion via parenteral nutrition on liver function was first time evaluated in rats in an ALI setting. The comparison of three forms of lipid emulsion in a rat model of acute lung injury was first time studied. The fish oil-based lipid emulsion decrease in PGE 2 and increase in LTB 4 was first time reported.

中文翻译：

---

在急性肺损伤之前用三种脂质乳剂预处理大鼠会影响肺和肝中细胞因子的产生和细胞凋亡。

背景技术重症患者罹患急性肺损伤（ALI）的风险更高，并且更经常需要肠胃外营养。我们试图研究用脂质乳剂预处理一周是否可以使ALI大鼠受益。方法使用脂多糖（LPS）诱导的ALI大鼠模型和技术，例如聚合酶链反应（PCR），酶联免疫吸附测定（ELISA）和末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）染色。结果LPS组血清中PGE2的产量最高，其次是脂内组，这两组的PGE2水平均显着高于其他组（P <0.05）。与LPS，Clinoleic或Omegaven组相比，脂质内调理导致LTB4的产生明显减少。与脂质体内相比，用亚油酸或欧米茄（Omegaven）预处理的大鼠显着降低了炎性介质（IL-1β，IL-6和TNF-α）的产生，减少了肺组织的细胞凋亡，在脂多糖（LPS）刺激下，欧米茄（Omegaven）大大改善了肝功能。结论在ALI环境中，用Omegaven或亚油酸进行的预处理在降低LPS刺激引起的细胞因子风暴和细胞凋亡的强度方面优于Intralipid，并且Omegaven另外还具有改善肝功能的潜力。本研究的结果为进一步研究ALI的分子机制（包括促炎因子产生的上下游途径）奠定了基础，寻找干预ALI发病机制的（小）分子，以将相关研究结果转化为ALI患者的临床获益。由于缺乏相关研究，特别是在ALI患者中使用Omegaven或Clinoleic仍具有不确定性。未来的研究必须特别关注给药途径和给药方式（肠内，肠胃外/推注与连续），确定欧米茄或亚油酸的最佳剂量，并确定最佳给药时间。重症患者罹患急性肺损伤（ALI）的风险更高，更经常需要肠胃外营养。首次在ALI环境中评估了通过肠外营养脂质乳剂对肝功能的影响。首次研究了三种形式的脂质乳剂在大鼠急性肺损伤中的比较。首次报道了鱼油基脂质乳液的PGE 2减少和LTB 4的增加。