长期食用植物源性 ω-3 脂肪酸可改善实验性缺血性脑卒中的结局。
Long-term dietary supplementation with plant-derived omega-3 fatty acid improves outcome in experimental ischemic stroke.
机构信息
Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland; Department of Internal Medicine, Cantonal Hospital of Baden, Baden, Switzerland.
Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland; First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.
出版信息
Atherosclerosis. 2021 May;325:89-98. doi: 10.1016/j.atherosclerosis.2021.04.005. Epub 2021 Apr 20.
BACKGROUND AND AIMS
Early revascularization -the gold standard therapy for ischemic stroke- is often withheld in the elderly population due to high risk of complications. Thus, safe and effective preventive and therapeutic options are needed. The plant-derived omega-3-fatty-acid alpha-linolenic-acid (ALA) has emerged as a novel cardiovascular-protective agent. As of yet, little is known about its potential therapeutic effects on stroke. We hereby aimed to investigate the impact of a clinically relevant long-term dietary intervention with ALA on stroke outcome.
METHODS
Six month-old C57BL/6 wildtype males were either fed an ALA-rich (high ALA) or a control diet (low ALA) for 12 months. At 18 months, brain ischemia/reperfusion was induced by transient middle cerebral artery occlusion (tMCAO). Stroke size and neurological function were assessed. Functional blood-brain-barrier-(BBB) permeability and protein expression were assessed by immunohistochemistry. Baseline inflammatory markers were measured at 18 months.
RESULTS
High ALA-fed animals displayed decreased circulating TNF-α levels and Neutrophil-to-Lymphocyte Ratios at 18 months. Stroke size and neurological dysfunction were significantly reduced in high ALA-fed animals. Coherently to the reduced stroke size, functional BBB integrity and occludin endothelial expression were maintained by high ALA supplementation. Additionally, ALA reduced endothelial activation and thus recruitment and activation of macrophages and resident microglia. Finally, high ALA diet reduced the expression of BBB-degrading and neurotoxic MMP-3 and MMP-9.
CONCLUSIONS
We demonstrate the beneficial effects of a clinically relevant and feasible dietary intervention with a safe and readily available compound in the setting of stroke. The protective effects observed with ALA supplementation may relate to blunting of inflammation and might pave the way for novel stroke treatments.
背景与目的
早期血运重建——缺血性脑卒中的金标准治疗——由于并发症风险高，在老年人群中常被推迟。因此，需要安全有效的预防和治疗选择。植物源性ω-3 脂肪酸α-亚麻酸（ALA）已成为一种新的心血管保护剂。然而，其对脑卒中的潜在治疗作用知之甚少。我们旨在研究临床相关的长期 ALA 饮食干预对脑卒中结局的影响。
方法
6 月龄 C57BL/6 野生型雄性小鼠分别给予富含 ALA（高 ALA）或对照饮食（低 ALA）12 个月。18 个月时，通过短暂性大脑中动脉闭塞（tMCAO）诱导脑缺血/再灌注。评估脑卒中大小和神经功能。通过免疫组化评估功能性血脑屏障（BBB）通透性和蛋白表达。在 18 个月时测量基线炎症标志物。
结果
高 ALA 喂养动物在 18 个月时表现出循环 TNF-α水平和中性粒细胞与淋巴细胞比值降低。高 ALA 喂养动物的脑卒中大小和神经功能障碍显著减轻。与脑卒中体积减小一致，高 ALA 补充维持了功能性 BBB 完整性和紧密连接蛋白内皮表达。此外，ALA 减少了内皮细胞的激活，从而减少了巨噬细胞和驻留小胶质细胞的募集和激活。最后，高 ALA 饮食降低了 BBB 降解和神经毒性 MMP-3 和 MMP-9 的表达。
结论
我们证明了在脑卒中背景下，临床相关且可行的 ALA 饮食干预具有有益作用。ALA 补充的保护作用可能与抑制炎症有关，并为新型脑卒中治疗方法铺平道路。
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