中文摘要
心肌缺血再灌注损伤(MIR)及其所致心律失常(与中医学“胸痹”、“心痛”、“心悸”等病症相似)是目前心血管疾病的主要致死原因,家庭与社会不堪重负。常用药物疗效不甚理想,和/或副作用明显。参芎注射液对MIR及心律失常等病症疗效确切、安全但机制不清。MIR损伤时机体通过调节能量感受器AMPK与营养感受器mTOR信号分子促进自噬的过度激活反而带来损害,因此对其进行干预是抗MIR的新策略。本项目在预实验基础上通过心肌细胞缺氧/复氧、离体心脏灌流和大鼠MIR模型,提出参芎注射液可能通过干预自噬PI3K-Akt-mTOR-Atg1、JNK1-Bcl-2-Beclin1、Ca2+/CaMKK-AMPK通路的多个关键蛋白,从多个层面调控自噬及心肌细胞离子通道,抑制过度自噬、钙超载、mPTP开放的科学假说,以期阐明活血、行气、化瘀中药防治“胸痹”、“心痛”、“心悸”的分子机制及现代科学内涵。
英文摘要
Myocardial ischemia reperfusion (MIR) and induced arrhythmia, which symptoms are similar to ‘chest impediment’, ‘heart pain’, ‘palpitations’ in traditional Chinese medicine, are the most lethal pathophysiological processes in cardiovascular diseases.It causes a heavily family and social economic burden. To date, the commonly prescribed drugs against myocardial ischemia reperfusion and induced arrhythmia merely bring about unsatisfactory effects, and/or possessing obvious side effects. The anti myocardial ischemia reperfusion and induced arrhythmias effects of Shenxiong Glucose Injection(SGI) had been firmly demonstrated except its mechanisms. Currently, it believed that the autophagy is excessively promoted under myocardial ischemia reperfusion by activating of energy receptor AMPK and nutrition receptor mTOR leading to endogenous injury. Therefore, it´s a new strategy to prevent excessive autophagy injury to against MIR. Based on our previous studies, the efficacy of SGI on myocardial ischemia reperfusion and induced arrhythmia are planned to be evaluated in this study target on PI3K-Akt-mTOR-Atg1、JNK1-Bcl-2-Beclin1、Ca2+/CaMKK-AMPK signaling pathways with myocardial ischemia/reoxygenation, langendorff and rat MIR models, and to investigate SGI effects on ion channels, calcium overload, mPTP and mitochondrial membrane potential with patch clamp and molecular biology technology to identify scientific hypothesis. This study can elucidate the mechanisms and scientific connotation of blood-activating, qi-moving, stasis resolving medicine SGI on ‘chest impediment’, ‘heart pain’ and ‘palpitations’ with different models in vitro and in vivo.
