花色苷及其代谢产物对神经细胞凋亡过程中PI3K/Akt信号途径的影响

Neuron apoptosis is one of major factors which lead to the brain aging. Preliminary animal experiments have confirmed that grape and mulberry anthocyanins contributed to brain aging inhibition and enhancing cognitive competence. This program aims to prevent neuron from apoptosis with anthocyanins in grape and mulberry. In this program, two models would be established. Digestive absorption and metabolism model simulating the metabolism process in vitro design to reveal the metabolism regime of anthocyanins; apoptosis model established on Aβ25-35 inducing PC12 neuron is to determine the anti-neuron apoptotic function of anthocyanins as well as the structure-activity, dose-effect and time-effect relationship. Furthermore, by investigating the expression and modification of the key proteins occurred in PI3K/Akt signal pathway and its downstream pathway. Based on these two modles, the mechanism and cell signaling pathway of anti-neuron apoptotic function of the anthocyanin and its metabolite would be illustrated detailedly. Above all, the program aims to provide scientific basis for establishing and generalizing a scientific diet to alleviate brain aging and protect brain health.

神经细胞凋亡是引起脑衰老的重要原因之一。动物实验已经初步证实，植物多酚对脑衰老、认知能力下降具有预防及治疗效果。本项目拟以葡萄、桑葚花色苷为试材，探究花色苷及其代谢产物对神经细胞的保护作用。项目研究拟构建花色苷消化、吸收、代谢模型，在体外模拟花色苷的代谢过程，以期发现其代谢规律；通过Aβ 25-35诱导的PC12神经细胞凋亡模型，验明花色苷对神经细胞凋亡的抑制效果，揭示它对神经细胞凋亡过程中PI3K/Akt信号途径及其下游一系列关键蛋白的表达差异，在转录及翻译水平上阐明花色苷代谢产物对神经细胞凋亡抑制作用的构效、量效、时效关系。项目研究基于上述两种研究模型，拟探明花色苷及其代谢产物对神经细胞保护作用的内在细胞信号途径及其作用机制，为今后建立并推广延缓脑衰老、维护脑健康的饮食干预方案提供科学依据。

本项目以食源性花色苷及其代谢产物对神经细胞凋亡的抑制作用及其机制为主要内容，构建了食源性花色苷消化—吸收—代谢模型，以及Aβ25-35诱导的PC12 神经细胞凋亡模型，在化学模拟体系和细胞凋亡模型基础上，运用HPLC-QTOF/MS 技术揭示了食源性花色苷的消化、吸收、代谢规律，采用细胞和分子生物学手段揭示花色苷及其代谢产物对神经细胞凋亡抑制作用的构效、量效、时效关系，以及凋亡进程中PI3K 信号通道关键蛋白的表达差异，最终在转录及翻译两个层面确定花色苷及其对神经细胞保护作用的内在细胞信号通路及作用机制。