基于MicroRNA-内质网应激-自噬轴探讨益气温阳活血利水法治疗心衰的机制

项目名称： 基于MicroRNA-内质网应激-自噬轴探讨益气温阳活血利水法治疗心衰的机制

项目编号： No.81473621

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 冼绍祥

作者单位： 广州中医药大学

项目金额： 72万元

中文摘要： 心衰的发病率稳步增加，自噬在心衰发病中的重要作用已开始受到广泛重视，深入探索自噬在心衰中作用的上游机制将有助于寻找到从自噬途径治疗心衰的上游靶点。最新研究证明miRNA和内质网应激在心衰的发病中均起着重要作用，miRNA-内质网应激-自噬轴在心衰的发病中发挥着重要作用，调节miRNA-内质网应激-自噬轴成为心衰防治的重要策略。益气温阳活血利水法是心衰的主要治法，研究证明其具有调节心肌细胞自噬，改善心功能等作用。本研究拟通过制备整体动物模型和培养原代细胞，利用免疫印迹、qPCR、腺病毒载体转染、透射电镜等方法，在细胞和整体水平研究心肌细胞miRNA-内质网应激-自噬轴在心衰的作用及机制，以及益气温阳活血利水法调节miRNA-内质网应激-自噬轴治疗心衰的作用。为益气温阳活血利水法治疗心衰提供新的理论依据和实验基础，为筛选调节miRNA-内质网应激-自噬轴治疗心衰的中药新药提供依据。

中文关键词： 微小RNA；内质网应激；自噬；心衰；益气温阳活血利水

英文摘要： The incidence of heart failure is steadily increasing. The important role of autophagy in heart failure has been paid much attention. To explore the mechanism of autophagy in heart failure will contribute to find the upstream targets to treatment heart failure. Recent studies demonstrated that both miRNA and endoplasmic reticulum stress (ER stress) had played an importannt role in HF. The miRNA -ERS axis mediated cardiomyocyte autophagy may play a significant role in HF. Therapies targeted against miRNA-ER stress-autophagy axis may become an imporant strategy in patients with HF. Preliminary study showed that the thearpy of benefiting qi and warming yang and activating blood can regulate cardiomyocyte autophagy and improve cardiac function. This research will explore the mechanism of miRNA-ER stress-autophagy axis in vivo and in vitro by using the different methods , such as Western Blot, qPCR, adenovirus vector transfection and transmission electron microscope(TEM) on the overall animal models and primary cells. The results of the research will provide new theoretical basis and experimental evidence for treating heart failure with benefiting qi and warming yang, activating blood and promoting diuresis. It can provide evidence on screening new traditional Chinese medicine compounds that can regulate the miRNA-ER stress-autophagy axis in heart failure.

英文关键词： MicroRNA;Endoplasmic reticulun stress;Autophagy;Heart failure;Benefiting qi;warming yang;activating blood and promoting diuresis