)：缺血性心脏病发展到心脏衰竭和恶性心律失常阶段，单一药物很难奏效，长期应用甚至出现严重毒副作用，而中药应用历史悠久，对于缺血性心脏病尚有一药多靶的作用特点。我们发现复方药物中的部分二咖啡酰奎宁酸区别于其他同类咖啡酰奎宁酸，是方剂保护心肌细胞、抗心律失常的药效物质，具有抗氧化应激诱导心肌细胞凋亡、抑制心肌细胞钠和钙电流、以及延长动作电作时程的作用。但针对该类化合物的研究重点集中在其多酚羟基结构相关的氧自由基清除作用，无法解释同类化合物在结构-活性上的差别。我们拟从中药多途径作用特点出发，以Nrf2/ARE介导的抗氧化应激转录后信号通路和心肌细胞离子通道调节为切入点，证明其心肌保护和抗心律失常的作用与多酚羟基的结构特点无关。阐明该类化合物抗氧化应激诱导心肌细胞凋亡与心肌离子通道调节作用的构效差别及其详细的作用机制。是对明确传统中药药理作用机制，解释复方药物组方科学内涵的一次有意义的尝试。

When the ischemic heart disease develops into the heart failure and malignant arrhythmia, the single drug hardly worked. Some of these chemical drugs will cause the serious side effects in long-term application. The Traditional Chinese medicine(TCM) has a very long history, which possesses the characteristics of safety, effectiveness and synergistic effects in the disease of cardiovascular system. In our previous works, some dicaffeoylquinic acids isolated from a Compound Chinese Herbs, as active ingredients in myocardial protection and antiarrhythmia, were proven effective to resist myocardial apoptosis induced with oxidative stress, prolong action potential duration of cardiocytes, and inhibit sodium and potassium currents. However, the researches on caffeoylquinic acids were still focused on its polyphenols hydroxyl structure for cleaning oxygen radical, which couldn't expiain their structure-activity differences. On the basis of the synergistic effects of TCM for the ischemic heart disease, we will screen and isolate active caffeoylquinic acids with the potential of the antioxidant stress damage and the Ion Channel regulation. For the active ingredients, we will get more into the mechanism of the Nrf2/ARE mediated signal transduction pathways and post-transcriptional gene regulations. We will explain that the myocardial protective and antiarrhythmic activities of the dicaffeoylquinic acids have nothing to do with their polyphenols hydroxyl structure, and elucidate the differences of structure-activity relationship and detailed mechanism. In this perspective, we believe this study will be a meaningful attempt to elucidate the therapeutic basis and pharmacological function mechanism of Traditional Chinese Medicine.

缺血性心脏病发展到心脏衰竭和恶性心律失常阶段，单一药物很难奏效，长期应用甚至出现严重毒副作用，而中药应用历史悠久，对于缺血性心脏病尚有一药多靶的作用特点。我们发现复方药物中的部分二咖啡酰奎宁酸区别于其他同类咖啡酰奎宁酸，是方剂保护心肌细胞、抗心律失常的药效物质，具有抗氧化应激诱导心肌细胞凋亡、抑制心肌细胞钠和钙电流、以及延长动作电作时程的作用。但针对该类化合物的研究重点集中在其多酚羟基结构相关的氧自由基清除作用，无法解释同类化合物在结构-活性上的差别。我们拟从中药多途径作用特点出发，以 Nrf2/ARE 介导的抗氧化应激转录后信号通路和心肌细胞离子通道调节为切入点，证明其心肌保护和抗心律失常的作用与多酚羟基的结构特点无关。阐明该类化合物抗氧化应激诱导心肌细胞凋亡与心肌离子通道调节作用的构效差别及其详细的作用机制。本项目研究发现咖啡酰奎宁酸对普萘洛尔模型大鼠的氧化应激、心率减慢等具有保护作用。本项目因负责人无法保证项目的正常执行，已经在2017年申请终止资助。