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短期输注鱼油乳剂后肺组织中n-3脂肪酸组成的改变可减轻炎症性血管反应。

Alteration of n-3 fatty acid composition in lung tissue after short-term infusion of fish oil emulsion attenuates inflammatory vascular reaction.

作者信息

Breil I, Koch T, Heller A, Schlotzer E, Grünert A, van Ackern K, Neuhof H

机构信息

Department of Anesthesiology, Faculty for Clinical Medicine Mannheim, University of Heidelberg, Germany.

出版信息

Crit Care Med. 1996 Nov;24(11):1893-902. doi: 10.1097/00003246-199611000-00021.

DOI:10.1097/00003246-199611000-00021
PMID:8917042
Abstract

OBJECTIVES

To investigate whether modulation of the fatty acid profile can be achieved by the short-term infusion of a fish oil emulsion which may attenuate the pulmonary response to inflammatory stimulation. Changes of fatty acid pattern in-lung tissue and perfusate were analyzed and correlated with physiologic data after a 3-hr infusion of fish oil in comparison with a soybean oil preparation.

DESIGN

Prospective, randomized, controlled trial.

SETTING

Experimental laboratory in a university teaching hospital.

SUBJECTS

Forty standard breed rabbits of either gender.

INTERVENTIONS

Isolated lungs from anesthetized rabbits were ventilated and recirculation-perfused (200 mL/min) with 200 mL of cell-free buffer solution to which either 2 mL of saline (control, n = 6), 2 mL of a 10% soybean oil preparation (n = 6), or 2 mL of a 10% fish oil emulsion (n = 6) were added. Samples of perfusate and lung tissue were collected for analysis of fatty acid composition. Tissue and perfusate fatty acid composition were analyzed by capillary gas chromatography. To study metabolic alterations in states of inflammatory stimulation, lungs of each group were stimulated with small doses of the calcium ionophore, A23187 (10(-8) M), during the 180-min lipid perfusion period and again after washing out the lipids by exchanging the perfusion fluid. Pulmonary arterial pressure and lung weight gain were monitored, and eicosanoids were analyzed in the perfusate.

MEASUREMENTS AND MAIN RESULTS

Free eicosapentaenoic acids increased several-fold in lung tissue and perfusate during a 3-hr infusion with fish oil. The intravenously administered n-3 fatty acids were rapidly hydrolyzed, as indicated by the appearance of substantial quantities of eicosapentaenoic acid in the perfusate free fatty acid fraction. This increase of perfusion levels of eicosapentaenoic acid was paralleled by an attenuated pressure increase and edema formation due to calcium ionophore challenge and an altered eicosanoid spectrum determined in the perfusate compared with soybean oil-treated lungs.

CONCLUSION

Short-term n-3 lipid application (fish oil emulsion) exerts anti-inflammatory effects on lung vasculature, which may be due to the metabolism of eicosapentaenoic acid resulting in the generation of less potent inflammatory eicosanoids.

摘要

目的

研究短期输注鱼油乳剂是否能够调节脂肪酸谱,进而减轻肺部对炎症刺激的反应。在输注鱼油3小时后,分析肺组织和灌注液中脂肪酸模式的变化,并将其与生理数据相关联,同时与大豆油制剂进行比较。

设计

前瞻性、随机、对照试验。

地点

大学教学医院的实验实验室。

对象

40只标准品种的兔子,雌雄不限。

干预措施

将麻醉兔子的离体肺进行通气,并以200 mL/分钟的速度用200 mL无细胞缓冲溶液进行再循环灌注,该溶液中分别添加2 mL生理盐水(对照组,n = 6)、2 mL 10%大豆油制剂(n = 6)或2 mL 10%鱼油乳剂(n = 6)。收集灌注液和肺组织样本以分析脂肪酸组成。通过毛细管气相色谱法分析组织和灌注液中的脂肪酸组成。为了研究炎症刺激状态下的代谢变化,在180分钟脂质灌注期间,用小剂量钙离子载体A23187(10⁻⁸ M)刺激每组的肺,在通过更换灌注液洗去脂质后再次刺激。监测肺动脉压和肺重量增加,并分析灌注液中的类花生酸。

测量指标和主要结果

在输注鱼油3小时期间,肺组织和灌注液中的游离二十碳五烯酸增加了数倍。静脉注射的n-3脂肪酸迅速水解,灌注液游离脂肪酸部分中大量二十碳五烯酸的出现表明了这一点。与大豆油处理的肺相比,二十碳五烯酸灌注水平的这种增加伴随着钙离子载体激发引起的压力增加和水肿形成的减轻,以及灌注液中类花生酸谱的改变。

结论

短期应用n-3脂质(鱼油乳剂)对肺血管系统具有抗炎作用,这可能是由于二十碳五烯酸的代谢导致产生的炎症性类花生酸活性降低。

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