基于线粒体凋亡途径探讨桂枝甘草汤抗心肌细胞凋亡改善心脏功能的机制研究

Heart failure (HF) is the end stage of a variety of cardiovascular diseases, the pathogenesis of which is diverse and complex. The last decade of research provided convincing evidence that the lack of myocardial energy caused by mitochondrial dysfunction may be an important event in the development of HF. We believed that the pathogenesis of HF in traditional Chinese medicine theory is heart yang deficiency, which has a commonality with the lack of myocardial energy in modern medicine theory. We used GuiZhiGanCao decoction, which is the ancestral prescription of Xingan Huayang theory, as a treatment of HF in clinical practice, and achieved good curative efficacy. We also found that GuiZhiGanCao decoction could effectively inhibit cardiomyocyte apoptosis, reduce Bax protein expression, increase Bcl-2 protein expression and increase mitochondrial membrane potential in doxorubicin (Dox) induced apoptosis of H9C2 cardiomyocytes. On the basis of previous work, we will use rats with HF as subjects, the structure and function of myocardial mitochondria and mitochondria apoptosis pathway as a cut-in point to explore the effects of Guizhi Gancao Decoction on inhibiting cardiomyocyte apoptosis and repairing mitochondrial function, which might be the modern biological basis of Guizhi Gancao Decoction improving cardiac function. The purpose of this study is also to enrich the modern medical evidence of heart yang deficiency treatment according with Xingan Huayang theory, and provide new ideas and new strategy for the clinical treatment of HF.

心力衰竭是多种心血管疾病的终末期阶段，其发病机制具有多样性和复杂性，近些年针对心力衰竭病理机制的研究证实线粒体功能障碍导致的心肌能量不足可能是该病发展过程中的重要事件。本课题组认为心力衰竭的中医根本病机心阳虚衰与现代医学的心肌能量不足具有共同性，并采用辛甘化阳配伍的祖方桂枝甘草汤治疗心力衰竭在临床实践中取得良好疗效。而且课题组前期工作发现在阿霉素诱导的H9C2心肌细胞凋亡模型中，桂枝甘草汤可以有效抑制心肌细胞凋亡、减少Bax蛋白表达、增加Bcl-2蛋白表达、提高线粒体膜电位，从而达到心肌保护作用。本研究在前期工作的基础上，以心力衰竭大鼠为研究对象，以心肌线粒体的结构、功能和线粒体凋亡途径为切入点，深入揭示桂枝甘草汤修复线粒体损伤、调节线粒体凋亡途径、抑制心肌细胞凋亡，改善心脏功能的现代生物学基础。并丰富和完善中医应用辛甘化阳法治疗心阳虚衰的现代医学证据，为心力衰竭的治疗提供有效策略。