Gilbert Kim, Bernier Judith, Godbout Roger, Rousseau Guy
Centre de biomédecine, Hôpital du Sacré-Cœur de Montréal, 5400 boul. Gouin Ouest, Montréal, PQ H4J 1C5, Canada.
Mar Drugs. 2014 Nov 13;12(11):5396-407. doi: 10.3390/md12115396.
We hypothesized that inflammation induced by myocardial ischemia plays a central role in depression-like behavior after myocardial infarction (MI). Several experimental approaches that reduce inflammation also result in attenuation of depressive symptoms. We have demonstrated that Resolvin D1 (RvD1), a metabolite of omega-3 polyunsaturated fatty acids (PUFA) derived from docosahexaenoic acid, diminishes infarct size and neutrophil accumulation in the ischemic myocardium. The aim of this study is to determine if a single RvD1 injection could alleviate depressive symptoms in a rat model of MI. MI was induced in rats by occlusion of the left anterior descending coronary artery for 40 min. Five minutes before ischemia or after reperfusion, 0.1 μg of RvD1 or vehicle was injected in the left ventricle cavity. Fourteen days after MI, behavioral tests (forced swim test and socialization) were conducted to evaluate depression-like symptoms. RvD1 reduced infarct size in the treated vs. the vehicle group. Animals receiving RvD1 also showed better performance in the forced swim and social interaction tests vs. vehicle controls. These results indicate that a single RvD1 dose, given 5 min before occlusion or 5 min after the onset of reperfusion, decreases infarct size and attenuates depression-like symptoms.
我们推测，心肌缺血诱导的炎症在心肌梗死（MI）后的抑郁样行为中起核心作用。几种减轻炎症的实验方法也会导致抑郁症状减轻。我们已经证明，源自二十二碳六烯酸的ω-3多不饱和脂肪酸（PUFA）的代谢产物Resolvin D1（RvD1）可减小缺血心肌中的梗死面积并减少中性粒细胞积聚。本研究的目的是确定单次注射RvD1是否能减轻MI大鼠模型中的抑郁症状。通过结扎左冠状动脉前降支40分钟在大鼠中诱导MI。在缺血前5分钟或再灌注后，将0.1μg的RvD1或赋形剂注入左心室腔。MI后14天，进行行为测试（强迫游泳试验和社交试验）以评估抑郁样症状。与赋形剂组相比，RvD1减小了治疗组的梗死面积。与赋形剂对照组相比，接受RvD1的动物在强迫游泳和社交互动测试中也表现更好。这些结果表明，在闭塞前5分钟或再灌注开始后5分钟给予单次RvD1剂量，可减小梗死面积并减轻抑郁样症状。
