基于实验动物和胃肠细胞模型研究荔枝原花青素的吸收、转运、排泄及构效关系

项目名称： 基于实验动物和胃肠细胞模型研究荔枝原花青素的吸收、转运、排泄及构效关系

项目编号： No.31501482

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 农业科学

项目作者： 李书艺

作者单位： 武汉轻工大学

项目金额： 19万元

中文摘要： 随着科学技术的日新月异，某些发达国家开始将原花青素作为一种重要的膳食补充剂来衡量国民的健康。本项目以南方特色水果荔枝为研究对象，联合多级柱层析色谱高效制备了其特有的原花青素低聚体，包括不同构象的黄烷醇单体、A-和B-型原花青素低聚物等。基于大鼠模型，研究荔枝果皮中主要的5种原花青素在生物体内的达峰时间、最大血药浓度、半衰期和消减速率，同时明确不同原花青素尿液代谢物的基本组成和靶标分配，以初步获取其吸收、转运、排泄的规律及构效关系。在体内试验的基础上，建立胃癌MKN-28和肠癌Caco-2细胞模型，模拟不同原花青素通过胃和小肠上皮细胞的吸收和转运。分别比较膜两侧pH梯度、转运时间、上样浓度和外源营养物质（乙醇、低聚糖）等因素对不同结构原花青素跨膜转运的影响；结合统计学分析，采用比较分子力场法（CoMFA）构建定量构象关系模拟函数，最终确定影响荔枝原花青素吸收和代谢的关键因素。

中文关键词： 荔枝原花青素；生物利用率；细胞转运；构效关系

英文摘要： Nowadays, procyanidins are considered a kind of dietary supplement by several developed countries to evaluate the physical conditions of citizens, since the science and technology is changing more and more quickly. In this research, litchi chinensis will be studied, which is a typical fruit in south of China and is used to prepare the representative procyanidin oligomers by multilevel column chromatography, including flavanol monomers, A- and B-type procyanidin oligomers. Depending on experimental animals, the bioavailability of main procyanidins in litchi pericarp will be discussed, in which we determine the peak time, maximum concentration, half-life and reduction rate of the compounds in rat plasma, and the composition of procyanidin metabolites in urine, in order to obtain the absorption, transport and excretion patterns of procyanidins, as well as their quantitative structure activity relationship (QSAR). Based on the results of in vivo experiment, we will establish an MNK-28 and a Caco-2 cell monolayer model to study the absorption and transport of different procyanidins through gastrointestinal epithelium cell. In the cell models, we will focus on the effect of pH gradient between apical and basolated side of cell, period of transport, concentration of samples and exogenous nutrients on the transport of procyanidins. At last, according to the statistical analysis and comparative molecular field analysis, a QSAR function will be calculated to describe the key factor of spatial structures, which intervenes the absorption and metabolism of procyanidins significantly.

英文关键词： litchi chinensis procyanidins;bioavailability;cell transport;quantitative structure activity relationship (QSAR)