Dietary fish oil and fish and borage oil suppress intrapulmonary proinflammatory eicosanoid biosynthesis and attenuate pulmonary neutrophil accumulation in endotoxic rats
Dietary fish oil and fish and borage oil suppress intrapulmonary proinflammatory eicosanoid biosynthesis and attenuate pulmonary neutrophil accumulation in endotoxic rats
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DOI：
10.1097/00003246-199707000-00023
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发表时间：
1997-07-01
影响因子：
8.8
通讯作者：
Karlstad, MD
中科院分区：
文献类型：
--
作者：
Mancuso, P;Whelan, J;Karlstad, MD
目的：促炎性二十烷基类化合物和细胞因子是急性肺损伤局部炎症的重要介质。我们确定了含有抗炎脂肪酸、二十碳五烯酸和伽马亚麻酸的肠内营养可以减少急性肺损伤大鼠肺内促炎性二十烷类化合物和细胞因子的合成以及肺中性粒细胞的聚集。设计：前瞻性、随机、对照、双盲研究。地点：一所大学医学中心的研究实验室。对象：雄性Long-Evans大鼠(250 G)。干预：大鼠随机分为三个饮食处理组，饲喂含有55.2%总热量的营养完整的饲料(300kcal/kg/d)，其中含有97%的玉米油、20%的鱼油、20%的鱼油。或者20%的鱼和20%的萝卜油，持续21天。第22天静脉注射肠炎沙门氏菌内毒素(10 mg/kg)或生理盐水后2小时行支气管肺泡灌洗。检测支气管肺泡灌洗液中白三烯B-4、白三烯C-4/D-4、血栓素B-2、前列腺素E-2、6-酮-前列腺素F-1α、肿瘤坏死因子-α和巨噬细胞炎性蛋白-2。测定和主要结果：与玉米油相比，鱼油、鱼油和琉球菜油肺组织中花生四烯酸含量较低，二十碳五烯酸和二十二碳六烯酸含量较高。与鱼油和玉米油相比，鱼油和芦荟油增加了γ-亚麻酸的脱饱和和拉长中间体--双高-γ-亚麻酸。与生理盐水组比较，内毒素组大鼠血中白三烯B-4、白三烯C-4/D-4、6-酮-前列腺素F-1α和血栓素B-2水平明显升高。与玉米油组相比，内毒素组大鼠肺泡灌洗液中白三烯B-4、白三烯C-4/D-4和血栓素B-2水平没有显著升高。内毒素处理组大鼠肺组织髓过氧化物酶活性较生理盐水处理组显著升高。然而，在内毒素作用下，无论是鱼油还是鱼油和罗非鱼油，肺组织髓过氧化物酶活性均显著低于玉米油。结论：与玉米油相比，膳食鱼油、鱼油和芦荟油可通过抑制肺泡灌洗液中促炎性二十烷类物质(而不是TNF-α和MIP-2)，减少中性粒细胞的聚集，从而减轻内毒素所致的急性肺损伤。
Objective: Proinflammatory eicosanoids and cytokines are important mediators of local inflammation in acute lung injury. We determined ii enteral nutrition with anti-inflammatory fatty acids, eicosapentaenoic acid, and gamma-linolenic acid would reduce the intrapulmonary synthesis of proinflammatory eicosanoids and cytokines and pulmonary neutrophil accumulation in a rat model of acute lung injury.Design: Prospective, randomized, controlled, double-blind study.Setting: Research laboratory at a university medical center.Subjects: Male Long-Evans rats (250 g).Interventions: Rats were randomly assigned to three dietary treatment groups and fed nutritionally complete diets (300 kcal/kg/day) containing 55.2% of the total calories from fat with either 97% corn oil, 20% fish oil, or 20% fish and 20% borage oil for 21 days. On day 22, bronchoalveolar lavage was performed 2 hrs after an intravenous injection of Salmonella enteritidis endotoxin (10 mg/kg) or saline. Bronchoalveolar ravage fluid was analyzed for leukotriene B-4, leukotriene C-4/D-4, thromboxane B-2, prostaglandin E-2, 6 keto-prostaglandin F-1 alpha, tumor necrosis factor (TNF)-alpha, and macrophage inflammatory protein-2 (MIP-2). Lung myeloperoxidase activity (a marker for neutrophil accumulation) and phospholipid fatty acid composition were also determined.Measurements and Main Results: Lung phospholipid concentrations of arachidonic acid were lower and the concentrations of eicosapentaenoic acid and docosahexaenoic acid were higher with fish oil and fish and borage oil as compared with corn oil. Dihomo-gamma-linolenic acid, the desaturated and elongated intermediate of gamma-linolenic acid, increased with fish and borage oil as compared with fish oil and corn oil. The levels of leukotriene B-4, leukotriene C-4/D-4, 6-keto-prostaglandin F-1 alpha and thromboxane B-2 with corn oil were significantly increased with endotoxin as compared with saline. In contrast to the corn oil group, endotoxin did not significantly increase bronchoalveolar lavage levels of leukotriene B-4, leukotriene C-4/D-4, and thromboxane B-2 above those of saline-treated rats with fish oil and fish and borage oil. Lung myeloperoxidase activity was significantly increased in endotoxin-treated rats compared with those rats given saline in all dietary treatment groups. However, lung myeloperoxidase activity was significantly lower with either fish oil or fish and borage oil as compared with corn oil after endotoxin. Although endotoxin increased the levels of TNF-alpha and MIP-2 with all dietary treatment groups as compared with saline-treated rats, there were no significant differences in the levels of either cytokine between the dietary treatment groups.Conclusions: These results indicate that dietary fish oil and fish and borage oil as compared with corn oil may ameliorate endotoxin-induced acute lung injury by suppressing the levels of proinflammatory eicosanoids;(but not TNF-alpha or MIP-2) in bronchoalveolar lavage fluid and reducing pulmonary neutrophil accumulation.