基于内质网应激及时相性变化研究抗纤益心方抑制扩张型心肌病大鼠心肌细胞凋亡的机制

内质网/线粒体亚细胞器损伤及联系障碍是导致心力衰竭（HF，心衰）的新分子机制，扩张型心肌病（DCM）的主要临床表现是HF，是一个一旦发生不断发展的疾病，因此早期干预至关重要。而心肌细胞凋亡是DCM发生HF的重要病理因素之一。我们前期研究已表明具有益气活血作用的抗纤益心方通过抑制DCM心衰大鼠心肌细胞凋亡而抗心肌纤维化、改善心室重构。由于DCM主要病理生理变化在心肌细胞，因此推测其抑制心肌细胞凋亡的作用机制之一应为通过调控心肌细胞内质网/线粒体钙转运及应激损伤信号通路。基于以上认识，我们采用呋喃唑酮灌胃给大鼠造成DCM心衰模型，结合AngⅡ诱导的原代培养的心肌细胞肥大模型，通过组织病理、定量PCR、Western杂交以及小RNA干扰等方法，探讨DCM心衰模型在其疾病发展过程中不同时间点细胞能量代谢障碍中内质网/线粒体亚细胞器损伤诱发凋亡的发生机制及抗纤益心方的最佳干预时间点和相关作用机制。

ER/mitochondrial subcellular damage and contact barriers lead to heart failure (HF, heart failure) of a new molecular mechanism of dilated cardiomyopathy (DCM) is the main clinical manifestations of HF, the event is a progressive disease, and therefore Early intervention is crucial. The myocardial apoptosis is one of the important factors in DCM occurrence of HF pathology. Our previous studies have shown that anti-fiber Yixin side has Yiqihuoxue effect by inhibiting apoptosis DCM and heart failure myocardium against myocardial fibrosis and improve ventricular remodeling. DCM is mainly due to changes in the pathophysiology of myocardial cells, so presumably one of the mechanisms which inhibit cardiomyocyte apoptosis regulation should be by myocardial cells within the endoplasmic reticulum / mitochondrial calcium transport and stress damage signaling pathways. Based on the above understanding, we use furazolidone gavage to rats with heart failure caused by DCM model, combined model of cardiac hypertrophy induced by AngII primary culture by histopathology, quantitative PCR, Western hybridization, and small RNA interference, to explore the heart of DCM failure model in its development of the disease process at different time points of cellular energy metabolism in the endoplasmic reticulum / mitochondrial subcellular damage induced pathogenesis and optimal intervention time point apoptosis Kangxian Yixin parties and related mechanisms.