基于构效关系揭示甘油磷脂型DHA的吸收利用机制

Marine phospholipids are rich in DHA, which can provide nutrition for brains and maintain their normal functions. Currently, this topic has become the research hotspot in food nutrition. Our previous studies have shown that the content of glycerophospholipids-DHA (GPs-DHA) with diverse structures in shellfish and other seafood was prominent. However, in vivo digestion and absorption as well as transport mechanism at the blood brain barrier (BBB) of dietary GPs-DHA are still not clear. This study is targeted at GPs-DHA with a hypothesis that the rates of DHA absorption in vivo and BBB permeabilities would be determined by different polar head groups and DHA regiochemical distributions. We adopt the scheme of ‘intragastric administration of GPs-DHA in rats, infusion of GP-DHA micelles in thoracic lymph duct-cannulated rats, and establishment of an in vitro BBB cell model’, and combine them with chromatography, spectroscopy, and mass spectrometry of the DHA content and GP composition in vivo, as well as BBB permeabilities of lyso-GPs-DHA in vitro. The present study intends to focus on exploring the effects of different polar head groups and DHA regiochemical distributions of GPs-DHA on the in vivo DHA absorption rates, as well as the in vitro BBB permeability regularity and transport process of lyso-GPs-DHA. Expected results would reveal the absorption and utilization mechanisms of GPs-DHA based on structure-activity relationship, and lay the theoretical foundations for the development and utilization of marine GPs-DHA.

海产品磷脂富含DHA，能够保证大脑营养和维持其正常功能，是当前食品营养学的研究热点。前期研究发现，贝类等海产品中甘油磷脂（GP）型DHA含量突出、结构多样，但膳食GP-DHA的体内消化吸收过程及血脑屏障（BBB）跨膜转运机制至今尚未明确。本项目以GP-DHA为对象，提出其不同极性头部和DHA化学位置分布决定DHA体内吸收率和BBB渗透性的假说。采用“大鼠灌胃GP-DHA、大鼠胸淋巴管插管灌注GP-DHA胶束、建立体外BBB细胞模型”的方案，结合色谱、光谱、质谱等方法分析动物体内的DHA含量、GP组成及溶血GP-DHA的BBB渗透量，拟重点探索极性头部和DHA化学位置差异对DHA体内吸收率的影响，及不同极性头部溶血GP-DHA的体外BBB渗透性规律和转运过程，从而基于构效关系揭示海产品GP-DHA的体内吸收利用机制。本研究将为海产品GP型DHA的深入开发利用奠定理论基础。

海产品磷脂富含DHA，能够保证大脑营养和维持其正常功能，是当前食品营养学的研究热点。前期研究发现，贝类等海产品中甘油磷脂（GP）型DHA含量突出、结构多样，但膳食GP-DHA的体内消化吸收过程及血脑屏障（BBB）跨膜转运机制至今尚未足够明确。本项目以GP-DHA为对象，提出其不同极性头部和DHA化学位置分布决定DHA体内吸收率和BBB渗透性的假说。采用“大鼠灌胃GP-DHA、大鼠胸淋巴管插管灌注GP-DHA胶束、建立体外BBB细胞模型”的方案，结合色谱、光谱等方法分析动物体内的DHA含量、GP组成及溶血GP-DHA的BBB渗透量，探索极性头部和DHA化学位置差异对DHA体内吸收率的影响，及不同极性头部溶血GP-DHA的体外BBB渗透性规律和转运过程。研究结果表明，sn-1位溶血甘油磷脂型DHA在淋巴液磷脂中的DHA回收率为游离型DHA的5倍；sn-1位溶血甘油磷脂型DHA胶束的加入，导致淋巴液高密度脂蛋白中的DHA回收率增加2倍；溶血甘油磷脂通过Mfsd2a蛋白跨血脑屏障转运DHA，且溶血磷脂酰胆碱结构更有利于Mfsd2a蛋白跨膜转运DHA。本研究将为海产品GP型DHA的深入开发利用奠定理论基础。此外，本研究开创了多相催化制备GP-DHA等结构磷脂的方法，将为后续研究提供极具潜力的研究思路。