Synthesis of Structured Phospholipids Containing Polyunsaturated Fatty Acid and Their Functional Evaluation

最近有报道称，磷脂酰丝氨酸(一种天然磷脂)和二十二碳六烯酸(DHA，一种多不饱和脂肪酸)对人脑神经系统具有积极的作用。正因为如此，它们作为有助于大脑健康的功能食品或医用材料吸引了人们的极大关注。本工作的目的是合成一种以DHA为脂肪酸残基的结构化磷脂酰丝氨酸，并对其在培养的神经细胞中的功能进行评价。1)以磷脂酰胆碱为原料，利用酶(磷脂酶A_2和磷脂酶D)结合化学脱酰化和酰化(酯化)的方法合成了三种结构磷脂。首次从大鼠胎脑中制备了1，2-didocosahexaenoyl-phosphatidylcholine(DDC)，神经细胞，并在1-oleoyl-2-docosahexaenoyl-phosphatidylserine(ODS).2)Brain/F-12混合培养液中进行了培养。加入各种化合物，包括合成的磷脂，通过检测细胞凋亡释放的乳糖脱氢酶活性来评价其对细胞死亡的保护或恶化作用。3)DDC、DDS和DS对培养条件下的细胞自然死亡无明显抑制作用。3)DDC、DDS和DS对培养条件下的神经元自然死亡无明显抑制作用。然而，观察到DDC、DDS和ODS对添加淀粉样蛋白β1-42蛋白所致的神经元损伤具有保护作用。

It has been recently reported that both phosphatidylserine (a kind of natural phospholipids) and docosahexaenoic acid (DHA, a kind of polyunsaturared fatty acids) have positive effects on human brain neural system. Because of them, they have attracted much the attention of people as functional foods or medical materials that contribute to brain health. The objective of this work is to synthesize a structured phosphatidylserine whose fatty acid residue is DHA, and to evaluate its function in cultured neural cells.1)Starting from phosphatidylcholine which is the most abundant phspholipid in nature, three kinds of structured phospholipids have been synthesized chomo-enzymatically : i.e., by using enzymes (phospholipases A_2 and D) combined with chemical deacylation and acylation (esterification). They are 1,2-didocosahexaenoyl-phosphatidylcholine(DDC), 1,2-didocosahexaenoyl-phsphatidylserine (DBS), and 1-oleoyl-2-docosahexaenoyl-phosphatidylserine(ODS).2)Brain neural cells were first prepared from rat fetal brain and cultured in DMEM/F-12 mixed medium. Adding various compounds including the synthesized phospholipids, protective or deteriorating effect on the cell death in the culture was evaluated by determining activity of lactose dehydrogenase released from apoptosis of the cells. Also, their protecting effect was evaluated from neuron damage induced by amyloid β protein in the culture.3)Depressive effects of DDC,DDS and ODS were not observed on natural cell death caused in the culture condition. However, it was observed that DDC,DDS and ODS protected from the neuron damage induced by added amyloid β1-42 protein.