SR-B1/CD36基因多态性及膳食维生素E摄入对DHA干预改善老年人认知功能效果的影响及其机制研究

Epidemiology study indicated the inverse association of DHA rich diet intake and the risk of AD. However, up to date, no convincing results were derived from the treatment of AD by using DHA supplementation. Except for the DHA dosage and experimental period, the differences of nutrients baseline status and genetic background of the participants might contribute to the various outcome of DHA dietary intervention. Our previous population based study indicated that MCI patients consumed less fish daily than control subjects. And MCI subjects have lower serum VE and erythrocyte n-3 PUFAs levels than control subjects. Moreover, variety of responds to dietary DHA dietary intervention was observed in human being or experimental animals, which indicated the possible contribution of genetic background to the outcome of DHA dietary intervention. Class B scavenger receptor (CD36 and SR-B1) were reported participating in the absorption and transport of VE and DHA in brain. Increasing evidences suggested that the mutation of CD36 and SR-B1 gene caused the abnormal of brain VE and DHA levels. These results indicated the interaction of CD36/SR-B1 gene polymorphism, VE and DHA with cognition in the elderly. In the current study, cross-sectional, case-control and follow-up studies were carried out to investigate the correlation among SR-B1/CD36 gene polymorphism, dietary VE and DHA consumption and cognitive function in the elderly. Besides, human beings and animal dietary intervention studies were applied to explore the combine effects of SR-B1/CD36 gene mutation and dietary VE consumption on the outcome of DHA dietary intervention in improving cognition. The study will provide scientific supports for the personalized dietary recommendation of DHA in the prevention of AD in the elderly.

流行病学调查结果表明，富含DHA 的饮食可降低AD的发生风险，然而DHA改善老年人认知功能的人群干预试验却未能获得预期结果。除干预剂量、时间等因素外，受试者的营养基线水平及遗传背景对干预结局的影响尚不清楚。课题组前期发现MCI患者每日鱼类摄入量及体内VE、n-3 PUFAs的水平明显低于对照组，提示VE及DHA在影响老年人认知功能过程中可能存在协同作用。此外，DHA干预效果的个体差异在人群及动物实验中均被观察到，提示了遗传因素对干预结局的影响。SRB1/CD36参与了脑内VE及长链脂肪酸的转运，且其基因变异可导致脑组织中VE及脂肪酸水平发生改变，推测VE、DHA及B类清道夫受体三者在影响脑功能过程中可能存在交互作用。本研究拟开展老年人现况调查、人群及动物饮食干预试验探讨VE、DHA、SRB1/CD36基因多态性与认知功能的关系，旨在为制定可预防AD的个性化DHA干预推荐量提供科学依据。

流行病学调查结果表明，富含DHA 的饮食可降低AD的发生风险，然而DHA改善老年人认知功能的人群干预试验却未能获得预期结果。除干预剂量、时间等因素外,受试者的营养基线水平及遗传背景对干预结局的影响尚不清楚。SRB1/CD36参与了脑内VE及长链脂肪酸的转运，且其基因变异可导致脑组织中VE及脂肪酸水平发生改变，推测VE、DHA及B类清道夫受体三者在影响脑功能过程中可能存在交互作用。本研究首先开展老年人群的现况调查群工作，通过基因分型对脂肪酸代谢相关基因SRB1/CD36进行了基因分型，采用统计分析的方法分析了不同SRB1/CD36型老年人VE及脂肪酸营养状况与认知功能的相关关系；开展了动物饮食干预试验探讨VE、DHA膳食摄入与AD模型动物学习记忆功能及AD相关病理变化的影响。研究结果表明，不同膳食VE摄入可以影响DHA干预改善AD 模型动物的学习记忆功能的效果，并且低VE摄入的AD模型动物在给予DHA干预时其学习记忆改善效果要优于高VE和中VE饮食的干预效果；长期（6个月以上）DHA饮食干预可以影响AD模型动物脑内脂肪酸谱，包括增加DHA水平，降低n-6PUFAs水平，并降低n-6/n-3 PUFA 比值，同时调控脑内参与脂肪酸摄取和代谢的CD36及SRB1基因和蛋白的表达。我们的结果提示了个体的脂代谢相关基因变异及脂溶性抗氧化维生素营养状况在影响老年人群认知功能过程中的相关关系，本研究对制定基于个体的遗传背景及营养状况的老年人群认知功能障碍及痴呆的干预策略提供了参考依据和证据支持。