Grimminger F, Grimm H, Führer D, Papavassilis C, Lindemann G, Blecher C, Mayer K, Tabesch F, Krämer H J, Stevens J, Seeger W
Department of Internal Medicine, Justus-Liebig University, Giessen, Germany.
Circulation. 1996 Jan 15;93(2):365-71. doi: 10.1161/01.cir.93.2.365.
omega-3 Fatty acids may have a major impact on immune responses involved in heart transplant rejection. We compared the effects of posttransplant intravenous supplementation with omega-3-rich versus omega-6-rich lipid emulsions on graft survival, plasma fatty acid profiles, and levels of arachidonic acid versus eicosapentaenoic acid-derived lipid mediators.
Inbred PVG and Wistar-Kyoto rats were used as donors and recipients, respectively, in a model of heterotopic heart transplantation. Animals received 9 g/kg body wt per day of either fish oil-derived (n = 8) or soybean oil-derived fat (n = 7) in the form of a continuously infused lipid emulsion; controls were sham-infused with saline (n = 8). Graft rejection was assessed by loss of activity of the transplant. The fish oil-derived preparation but not that originating from soybean oil caused an increase in total and free plasma fatty acids. Substantial quantities of eicosapentaenoic acid and docosahexaenoic acid appeared in the free fatty acid fraction, surpassing those of arachidonic acid. Ex vivo stimulation of neutrophils with the Ca2+ ionophore A23187 demonstrated an increase in 5-series leukotriene (LT) generation in animals undergoing omega-3 lipid infusion (LTB5, omega-oxidation products of LTB5, LTA5 secretion), with 5-series/4-series LT ratios ranging between 0.08 and 0.36. Ratios of TX B3/B2 liberated from ex vivo stimulated platelets even approached 1:1 in omega-3 supplemented rats. Graft survival was 7.6 +/- 0.3 (mean +/- SEM) days in saline-infused, 10.4 +/- 0.7 in omega-6 lipid-infused, and 12.9 +/- 0.4 in omega-3 lipid-infused animals.
Posttransplant intravenous alimentation with fish oil-derived lipid emulsions prolongs heart transplant survival in excess to omega-6 lipids. Profound changes in fatty acid profiles and lipid mediator generation may underlie this finding.
ω-3脂肪酸可能对心脏移植排斥反应中的免疫应答产生重大影响。我们比较了移植后静脉补充富含ω-3与富含ω-6的脂质乳剂对移植物存活、血浆脂肪酸谱以及花生四烯酸与二十碳五烯酸衍生的脂质介质水平的影响。
在异位心脏移植模型中，近交系PVG大鼠和Wistar-Kyoto大鼠分别用作供体和受体。动物每天接受9 g/kg体重的鱼油来源（n = 8）或大豆油来源的脂肪（n = 7），以持续输注脂质乳剂的形式；对照组用生理盐水进行假输注（n = 8）。通过移植活性丧失评估移植物排斥反应。鱼油来源的制剂而非大豆油来源的制剂导致总血浆脂肪酸和游离血浆脂肪酸增加。大量的二十碳五烯酸和二十二碳六烯酸出现在游离脂肪酸部分，超过了花生四烯酸。用Ca2+离子载体A23187对中性粒细胞进行体外刺激显示，接受ω-3脂质输注的动物中5系列白三烯（LT）生成增加（LTB5、LTB5的ω-氧化产物、LTA5分泌），5系列/4系列LT比率在0.08至0.36之间。在补充ω-3的大鼠中，体外刺激血小板释放的TX B3/B2比率甚至接近1:1。生理盐水输注组移植物存活时间为7.6±0.3（平均值±标准误）天，ω-6脂质输注组为10.4±0.7天，ω-3脂质输注组为12.9±0.4天。
移植后静脉输注鱼油来源的脂质乳剂可使心脏移植存活时间延长，超过ω-6脂质。脂肪酸谱和脂质介质生成的深刻变化可能是这一发现的基础。
