Department of Pediatrics, Juntendo University School of Medicine, Tokyo, Japan.
Neuropathology. 2010 Dec;30(6):597-605. doi: 10.1111/j.1440-1789.2010.01114.x.
Hypoxic-ischemic encephalopathy due to neonatal asphyxia is one of the most important causes of delayed neurological development. Prolonged neuronal apoptosis plays an important role in the processes contributing to neuronal degeneration. Docosahexaenoic acid (DHA), a major component of brain membrane phospholipids, prevents neuronal cell apoptosis and plays an important role as an anti-oxidant agent. We investigated the neuroprotective and anti-oxidant effects of maternal DHA supplementation during pregnancy in a model of neonatal hypoxic-ischemic encephalopathy. Pregnant rats were randomly assigned to two experimental groups: a control group or a DHA-enriched diet group. Hypoxic-ischemic encephalopathy was produced by left common carotid artery occlusion and exposure to 8% oxygen for 1.5 h. TUNEL assay, immunohistochemistry for caspase-3 and 8-hydroxy-deoxyguanosine (8-OHdG), and Western blot for caspase-3 were performed at postnatal days 8, 10 and 14. Fatty acid composition of brain was estimated on postnatal day 7. Maternal diet clearly influenced brain fatty acid composition in pups. Numbers of apoptotic neuronal cells and 8-OHdG immunoreactivity were significantly decreased in the DHA-enriched group. Our findings indicate that maternal DHA-enriched diet during pregnancy provides neuroprotection by inhibiting oxidative stress and apoptotic neuronal death. Dietary supplementation of DHA during pregnancy may thus be beneficial in preventing neonatal brain injury.
由于新生儿窒息导致的缺氧缺血性脑病是导致神经发育迟缓的最重要原因之一。延长的神经元凋亡在导致神经元变性的过程中起着重要作用。二十二碳六烯酸(DHA)是脑膜磷脂的主要成分之一,可防止神经元细胞凋亡,并作为抗氧化剂发挥重要作用。我们研究了在新生儿缺氧缺血性脑病模型中,孕期补充母体 DHA 对神经的保护和抗氧化作用。将怀孕的大鼠随机分为两组:对照组或富含 DHA 的饮食组。通过左颈总动脉闭塞和暴露于 8%的氧气 1.5 h 来制造缺氧缺血性脑病。在出生后第 8、10 和 14 天进行 TUNEL 测定、半胱氨酸天冬氨酸蛋白酶-3(caspase-3)和 8-羟基脱氧鸟苷(8-OHdG)的免疫组织化学染色以及 caspase-3 的 Western blot。在出生后第 7 天估计大脑的脂肪酸组成。母体饮食明显影响了幼鼠大脑的脂肪酸组成。富含 DHA 的组中,凋亡的神经元细胞数量和 8-OHdG 免疫反应性明显减少。我们的研究结果表明,孕期母体富含 DHA 的饮食通过抑制氧化应激和凋亡性神经元死亡提供神经保护作用。因此,孕期补充 DHA 可能有益于预防新生儿脑损伤。