五脏温阳化瘀汤对PI3K/Akt-mTOR通路介导动脉粥样硬化型血管性痴呆自噬与凋亡的效应机制

项目名称： 五脏温阳化瘀汤对PI3K/Akt-mTOR通路介导动脉粥样硬化型血管性痴呆自噬与凋亡的效应机制

项目编号： No.81460720

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 唐农

作者单位： 广西中医药大学

项目金额： 47万元

中文摘要： 动脉粥样硬化(AS)型血管性痴呆(VaD)是在AS的病理基础上出现脑功能障碍，以海马CA1区为主的神经细胞死亡产生获得性智能损害综合征。其中医病机本质是阳化不足，阴化太过。前期大量临床实践及实验研究证实五脏温阳化瘀汤治疗AS型VaD，疗效确切,且具有抗氧化作用。最新研究表明VaD与PI3K/Akt-mTOR通路调控神经细胞的凋亡和自噬关系密切。我们认为五脏温阳化瘀汤可能通过调节PI3K/Akt-mTOR通路介导AS型VaD自噬与凋亡而保护神经细胞。本项目通过复制AS型VaD大鼠模型，电镜观察海马CA1区神经细胞的自噬体；免疫组化、RT-PCR、Western Blot等检测PI3K/Akt-mTOR通路及其下游自噬与凋亡相关蛋白Beclin-1、LC3、Caspase-9、3及Bcl-2等表达，探讨五脏温阳化瘀汤干预AS型VaD的效应机制，为揭示中医阳化气、阴成形理论提供科学依据。

中文关键词： 五脏温阳化瘀汤；血管性痴呆；自噬；凋亡；信号通路

英文摘要： Atherosclerosis (AS) vascular dementia (VaD) has brain dysfunction based on the pathogenesis of AS, it is also an acquired intelligence injury syndrome which mainly caused by the neuronal cell death in hippocampal CA1 area. The TCM fundamental pathogenesis of this disease is Deficiency-Yang and Excess-Yin. Extensive clinical practice and experimental studies confirmed that Wuzangwenyanghuayu Decoction had antioxidant effect and curative effect on AS-VaD. The latest research showed that the PI3K/Akt-mTOR pathway regulated the neuronal apoptosis and autophagy，which was closely related to the VaD. We Suppose that Wuzangwenyanghuayu Decoction maybe protect the nerve cell by adjusted the regulation of autophagy and apoptosis which mediated by PI3K/Akt-mTOR pathways in AS-VaD. Our project using copying AS-VaD rat model to observe the hippocampal CA1 neurons autophagy in electron microscopy; and then testing the expression of PI3K/Akt-mTOR pathway downstream autophagy and apoptosis associated protein Beclin-1, LC3, Caspase-9, Caspase-3 and Bcl-2 by immunohistochemistry, RT-PCR and Western Blot methods. The purpose of our project is to explore the effector mechanism of Wuzangwenyanghuayu Decoction treated on AS-VaD and provide a scientific basis for the TCM theory Yang convert pneuma, Yin become entity.

英文关键词： WuZangWenYangHuaYuDecoction;Vascular Dementia;Autophagy;Apoptosis;Signal Pathway