Amissi Said, Boisramé-Helms Julie, Burban Mélanie, Rashid Sherzad K, León-González Antonio J, Auger Cyril, Toti Florence, Meziani Ferhat, Schini-Kerth Valérie B
UMR CNRS 7213, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, 74, route du Rhin, 67401, Illkirch, France.
EA 7293, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Faculté de Médecine, Université de Strasbourg, Strasbourg, France.
Lipids. 2017 Mar;52(3):235-243. doi: 10.1007/s11745-016-4225-y. Epub 2017 Jan 2.
Lipid emulsions for parenteral nutrition are used to provide calories and essential fatty acids for patients. They have been associated with hypertriglyceridemia, hypercholesterolemia, and metabolic stress, which may promote the development of endothelial dysfunction in patients. The aim of the present study was to determine whether five different industrial lipid emulsions may affect the endothelial function of coronary arteries. Porcine coronary artery rings were incubated with lipid emulsions 0.5, 1, or 2% (v/v) for 30 min before the determination of vascular reactivity in organ chambers and the level of oxidative stress using electron paramagnetic resonance. Incubation of coronary artery rings with either Lipidem, Medialipid containing long- and medium-chain triacylglycerols (LCT/MCT), or SMOFlipid containing LCT, MCT, omega-9, and -3, significantly reduced the bradykinin-induced endothelium-dependent relaxation, affecting both the nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) components, whereas, Intralipid containing LCT (soybean oil) and ClinOleic containing LCT (soybean and olive oil) did not have such an effect. The endothelial dysfunction induced by Lipidem was significantly improved by indomethacin, a cyclooxygenase (COX) inhibitor, inhibitors of oxidative stress (N-acetylcysteine, superoxide dismutase, catalase) and transition metal chelating agents (neocuproine, tetrathiomolybdate, deferoxamine and L-histidine). Lipidem significantly increased the arterial level of oxidative stress. The present findings indicate that lipid emulsions containing LCT/MCT induce endothelial dysfunction in coronary artery rings by blunting both NO- and EDH-mediated relaxations. The Lipidem-induced endothelial dysfunction is associated with increased vascular oxidative stress and the formation of COX-derived vasoconstrictor prostanoids.
肠外营养用脂质乳剂用于为患者提供热量和必需脂肪酸。它们与高甘油三酯血症、高胆固醇血症和代谢应激有关，这可能会促进患者内皮功能障碍的发展。本研究的目的是确定五种不同的工业脂质乳剂是否会影响冠状动脉的内皮功能。在使用电子顺磁共振测定器官腔中的血管反应性和氧化应激水平之前，将猪冠状动脉环与0.5%、1%或2%（v/v）的脂质乳剂孵育30分钟。用Lipidem、含有长链和中链三酰甘油（LCT/MCT）的Medialipid或含有LCT、MCT、ω-9和-3的SMOFlipid孵育冠状动脉环，会显著降低缓激肽诱导的内皮依赖性舒张，影响一氧化氮（NO）和内皮依赖性超极化（EDH）成分，而含有LCT（大豆油）的Intralipid和含有LCT（大豆油和橄榄油）的ClinOleic则没有这种作用。环氧化酶（COX）抑制剂吲哚美辛、氧化应激抑制剂（N-乙酰半胱氨酸、超氧化物歧化酶、过氧化氢酶）和过渡金属螯合剂（新亚铜试剂、四硫代钼酸盐、去铁胺和L-组氨酸）可显著改善Lipidem诱导的内皮功能障碍。Lipidem显著增加了动脉氧化应激水平。目前的研究结果表明，含有LCT/MCT的脂质乳剂通过减弱NO和EDH介导的舒张作用，诱导冠状动脉环内皮功能障碍。Lipidem诱导的内皮功能障碍与血管氧化应激增加和COX衍生的血管收缩性前列腺素的形成有关。
