稳心中药组分交互整合干预潜在恶性心律失常的效应特点及其机制

Traditional Chinese medicine plays an important role in the prevention and treatment of diseases when it is properly used in clinical practice. However, there is currently no systematic way to test the effectiveness of Chinese medicine. Therefore, the findings in this study may be used to guide the clinical use of some Chinese medicines. Potentially malignant arrhythmia is a condition for which biomedicine could be of little help. The Chinese patented medicine Wen Xin Granule has been used for potentially malignant arrhythmias (ventricular and atrial arrhythmias) and its effectiveness has been confirmed in a number of cases in a randomized, double blind trial. The underlying mechanism of action could be attributed to the synergetic effects of Wen Xin Granule through its multiple active ingredients on multiple-targets, thus various aspects of the physiological functioning are well balanced and adjusted. In this study, concepts and methods from evidence-based medicine, systematic pharmacology and bioinformatics will be determined in both in-vitro, whole heart and whole animal experiments. A small-sample clinical study is also planned in patients with ventricular premature beat and paroxysmal atrial fibrillation. The aims of the study were to identify the characteristics of the effects of Wen Xin Granule on potentially malignant arrhythmias. Tools and techniques such as patch clamp, laser confocal microscopy and electrophysiological study will be used in experiments with animal and isolated heart models to explore possible involvement of cellular signal transduction, ion channels and other structures, so as to explain the multi-target mechanisms and the effectiveness of Wen Xin Granules for treating potentially malignant arrhythmias of various mechanisms, while highlighting the direct or indirect therapeutic role of its major active components and the synergetic effects of some of its ingredients. This study will provide evidence from the perspective of animal research for the scientific and rational clinical application of Chinese medicine, or even for the "precisely-targeted use of Chinese medicine", and bring along novel ideas for the basic research of Chinese medicine...

中医药临床应用得当，可在防治疾病中发挥重要作用，然而中医药作用如何科学表达以确保临床科学应用，目前并不十分清楚。潜在恶性心律失常是中医临床确有疗效而西药尚未解决的临床难题，已证实稳心颗粒干预潜在恶性心律失常（室性、房性心律失常）临床有效，可能是其主要药效组分交互整合，发挥多向调节整合作用的结果。本项目拟从临床、整体动物、离体三个水平切入，采用循证医学、系统药理学、生物信息学等理念、方法，募集室早和阵发性房颤人群，进行目的明确、小样本的规范临床研究，揭示稳心中药干预潜在恶性心律失常的效应特点；复制整体动物和离体心脏模型，采用膜片钳、激光共聚焦、电生理等技术，结合细胞信号转导、离子通道和心脏结构，阐明稳心中药治疗潜在恶性心律失常的多向作用机制，突出稳心中药主要药效组分交互整合发挥间接直接效应的特色。本研究将为中医药临床科学合理应用，乃至“精准用药”提供实验依据，为中医药基础研究带来新思路。

本项目针对中医临床确有疗效、西药难以解决的潜在恶性心律失常的关键科学问题，以临床广泛应用的中成药稳心颗粒为模型药物，从临床、整体、离体三个层次着手，采用循证医学、系统药理学、生物信息学等理念、方法和系列关键技术，揭示了稳心中药干预潜在恶性心律失常“稳心合律”的临床效应特点，阐明了稳心中药治疗潜在恶性心律失常“多离子通道——非离子通道”的多向作用机制，彰显了稳心中药主要组分交互整合“多因微效”发挥间接直接效应的特色，最终为促进中医药作用的科学表达以确保临床精准应用提供了研究范例。具体成果体现在三个方面：1.阐释了基于“多离子通道——非离子通道”中药稳心合律的科学内涵：发现稳心颗粒对多种原因诱导的心律失常均有效，为直接、间接地发挥整合效应；2.发现了稳心颗粒对房颤具有选择性：抑制房颤呈现明确的量效关系，且不致心律失常；3.发现了稳心颗粒整合调律的网络效应机制，归因于其主要药效组分的各自贡献度：各司其责，与网络靶标相呼应；具有多因微效特点，因而安全性佳。项目组共发表相关学术论文25篇，其中SCI收录19篇，中文核心期刊6篇。单篇最高影响因子文章已在Redox biology （5年IF 9.02）online，单篇最高他引55次。培养国家杰出青年科学基金获得者1名、国家万人计划科技领军人才1名，北京市青拔1名，北京市科技新星2名，中华中医药学会青年托举人才（A类）2名。获中医药国际贡献奖。本项目研究证据被纳入中国生物医学工程学会心律失常分会、中国中西医结合学会脑心同治专业委员会共同组织专家制定、发布的《中医药抗心律失常专家共识》，并在临床上推广应用。