补阳还五汤维系巨噬细胞适度自噬而稳定动脉粥样硬化易损斑块的机制研究

项目名称： 补阳还五汤维系巨噬细胞适度自噬而稳定动脉粥样硬化易损斑块的机制研究

项目编号： No.81460612

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： 刘玉晖

作者单位： 江西中医药大学

项目金额： 48万元

中文摘要： 如何提高动脉粥样硬化(AS)易损斑块的稳定性是预防急性冠脉综合征猝死的关键。斑块内巨噬细胞基础性自噬可保护其免受各种应激物影响，而出现异常自噬将导致巨噬细胞表型改变，促进斑块内炎症因子释放破坏斑块的稳定性。研究显示，PI3K -Akt-mTOR分子通路是激活自噬主要调控通路，而巨噬细胞自噬除此之外，还与Rho激酶A、MAPK、ERK等信号转导通路的活化/磷酸化有关。寒凝、气滞、血瘀阻于心之络脉是易损斑块的病机，前期国家自然基金资助项目发现益气活血通络经方补阳还五汤明显缩小AS斑块面积、减轻AS病变与抑制RhoA、 MAPK、ERK1/2等信号通路磷酸化有关。本项目拟在前期基础上，通过ApoE-/-小鼠易损斑块模型与巨噬细胞炎症模型相结合，探讨补阳还五汤稳定易损斑块与斑块内巨噬细胞自噬及表型变化的关联及调控机制，揭示其在提高AS易损斑块稳定性中的作用及调控机制，为治疗AS提供新思路、新靶点。

中文关键词： 动脉粥样硬化；补阳还五汤；易损斑块；巨噬细胞自噬；信号通路

英文摘要： How to improve the stability of vulnerable plaque of atherosclerosis (AS) is the key point to prevent sudden death in acute coronary syndrome. Plaque macrophages' basal autophagy may protect it from the effects of stress, and the abnormal autophagy leads to macrophage phenotype changed, promote the inflammatory factor release increased plaque instability plaque. Research shows that, PI3K - Akt-mTOR pathway is the main pathway to activate autophagy, but autophagy of macrophages in addition with the Rho kinase A, MAPK, ERK and other signal transduction pathway activation / phosphorylation related. Cold and qi stagnation blood stasis in the heart of the collaterals are the pathogenesis of vulnerable plaque, supported by the National Natural Science Foundation discovered Yiqi Huoxue Tongluo prescription Buyang Huanwu decotion significantly reduced AS plaque area, reduced the AS lesion and inhibited RhoA, MAPK, ERK1/2 phosphorylation. Upon on these foundation the project will investigate the association Buyang Huanwu decotion to stabilize the vulnerable plaques and plaque phenotype changes of macrophages autophagy and regulation mechanism, which through the ApoE-/-mouse model of vulnerable plaque and macrophage inflammatory model, to reveal that Buyang Huanwu decotion in enhancing the role of AS in vulnerable plaque stability and regulation mechanism, to provide new ideas, new target for the treatment of AS.

英文关键词： atherosclerosis;Buyanghuanwu decotion;unstable plaque;macrophages autophagy;signal pathway