Institut de Pharmacologie Moléculaires et Cellulaires-UMR6097, C.N.R.S, 06560 Valbonne, France.
Pharmacol Res. 2010 Mar;61(3):226-33. doi: 10.1016/j.phrs.2009.12.007. Epub 2009 Dec 29.
Populations of Western countries are severely deficient in omega-3 intake, both in the form of alpha-linolenic acid (ALA) and the Long Chain derivatives (LC-n-3), Eicosa-Pentaenoic-Acid and Docosa-Hexaenoic-Acid. Omega-3 insufficiency is a risk factor for cardiovascular and cerebral diseases such as coronary heart disease and stroke. Stroke is a major cause of mortality and morbidity, and induces a significant socioeconomic cost and a marked increase in patient/family burden. To date, preventive treatments and neuroprotective drugs identified in preclinical studies failed in clinical trials, in part because of an inability to tolerate drugs at neuroprotective concentrations. Therefore testing alternative protective strategies, such as functional foods/nutraceuticals, are of considerable interest. We have previously demonstrated that a single injection of ALA reduced ischemic damage by limiting glutamate-mediated neuronal death, whereas repeated injections displayed additive protective benefits as a result of increased neurogenesis, synaptogenesis and neurotrophin expression. Because intravenous injections are not a suitable long-term strategy in humans, the present study investigated the effect of ALA supplementation by an experimental diet containing rapeseed oil (RSO, a rich source of ALA) as the only source of lipids for stroke prevention. We tested several experimental diets which included 5, 10, and 20% RSO-enriched diet and feeding paradigms (fresh diet was provided once or twice a week for 4 or 6 weeks). Our results showed that ALA supplemented diets are more sensitive to lipid peroxidation than a regular chow diet. Because the diet affected feeding behavior and animal growth, we defined concrete guidelines to investigate the effect of omega-3 supplementation on neuropathology. Among the different sets of experiments, animals fed with 10% and 20% RSO-enriched diet displayed a reduced mortality rate, infarct size and increased probability of spontaneous reperfusion in the post-ischemic period. In addition, a drastic reduction of lipid peroxidation levels was observed in the ischemic brain of RSO-fed animals. Overall, our findings provide new insights into the potential of employing rapeseed oil as a functional food/nutraceutical aiding in stroke prevention and protection.
西方国家的人群在 ω-3 摄入方面严重不足，无论是 α-亚麻酸（ALA）还是长链衍生物（LC-n-3）、二十碳五烯酸（Eicosa-Pentaenoic-Acid）和二十二碳六烯酸（Docosa-Hexaenoic-Acid）形式。ω-3 不足是心血管和脑疾病（如冠心病和中风）的一个风险因素。中风是死亡率和发病率的主要原因，会导致显著的社会经济成本和患者/家庭负担显著增加。迄今为止，在临床前研究中确定的预防性治疗和神经保护药物在临床试验中失败了，部分原因是无法耐受神经保护浓度的药物。因此，测试替代保护策略，如功能性食品/营养保健品，具有相当大的兴趣。我们之前已经证明，单次注射 ALA 通过限制谷氨酸介导的神经元死亡来减少缺血性损伤，而重复注射由于增加神经发生、突触形成和神经营养因子表达而显示出附加的保护益处。由于静脉内注射不是人类的一种合适的长期策略，因此本研究通过含有油菜籽油（RSO，ALA 的丰富来源）的实验饮食来研究 ALA 补充对中风预防的影响，该实验饮食是唯一的脂质来源。我们测试了几种实验饮食，包括 5%、10%和 20%的 RSO 丰富饮食和喂养方案（每周提供一次或两次新鲜饮食，持续 4 或 6 周）。我们的结果表明，ALA 补充饮食比常规饮食更容易受到脂质过氧化的影响。由于饮食会影响进食行为和动物生长，我们制定了具体的指导方针来研究 ω-3 补充对神经病理学的影响。在不同的实验组中，喂食 10%和 20% RSO 丰富饮食的动物死亡率、梗塞面积降低，并且在缺血后期间自发再灌注的可能性增加。此外，在 RSO 喂养动物的缺血大脑中观察到脂质过氧化水平的急剧降低。总的来说，我们的发现为将油菜籽油作为功能性食品/营养保健品用于中风预防和保护提供了新的见解。
