复方丹七片基于脂肪酸ß氧化FAT/CD36-CPT1A通路促进大鼠心肌缺血后血管新生的机制研究

The morbidity and mortality of coronary heart disease rank the first in the world. The treatment nature of coronary heart disease is the "therapeutic angiogenesis", which could promote the establishment of collateral circulation in ischemic region and increase blood flow supply. Researches in our lab have shown that Danqi Pill (DQP) could significantly protect myocardial functions and improve lipid metabolism disorders induced by myocardial ischemia, but the effects of DQP on angiogenesis and the molecular mechanism have not been elucidated. In this study, we will construct the myocardial ischemia models in rats. Based on FAT/CD36-CPT1A pathway of fatty acid oxidation (FAO), we will investigate the effects of DQP on angiogenesis. We also evaluate the effects of CPT1A on the angiogenesis by experimenting on rats and cell models. Danqi Pill is selected as the research object and pharmacological techniques are used in this study. FAT/CD36-CPT1A pathway is the starting point to explore the effects of DQP on angiogenesis. This study is of significant importance and may provide new mechanistic insights into angiogenesis and valuable information for better understanding the traditional Chinese medicine theory and promote the research and clinical treatment of Chinese medicine.

世界范围内冠心病的发病率与死亡率都高居首位，治疗冠心病最根本的原则是改善缺血组织的血流供给。通过“治疗性的血管生成”，促进缺血区域侧支循环的建立，增加血流供应，从而达到治疗疾病的目的。实验室之前的工作表明丹七片能够显著保护心肌功能，改善心肌缺血诱导的脂质代谢紊乱，但对心肌缺血后血管新生的影响及其作用机制尚未阐明。本课题将会：1）构建大鼠心肌缺血的动物模型，明确复方丹七片对大鼠心肌缺血后血管新生的影响；2）基于脂肪酸ß氧化的FAT/CD36-CPT1A通路，探究复方丹七片促进血管新生的作用机制；3）结合体内、体外模型多角度探究脂肪酸ß氧化的关键限速酶CPT1A对内皮血管新生的影响。本课题选用复方丹七片为研究对象，运用药理学实验技术，深入探究复方丹七片促血管新生的机制及抗心肌缺血的作用，深化对冠心病发病机制的认识，为缺血性疾病的防治提供新的研究思路，对促进中药研究与临床治疗均具有重要意义。

世界范围内冠心病的发病率与死亡率都高居首位，治疗冠心病最根本的原则是改善缺血组织的血流供给。通过“治疗性的血管生成”，促进缺血区域侧支循环的建立，增加血流供应，从而达到治疗疾病的目的。本课题：1）成功构建了左冠状动脉前降支结扎诱导的心肌缺血大鼠模型，发现丹七片对心肌缺血大鼠心脏功能具有保护作用，同时能够促进梗死边缘区域的血管新生；2）构建了H2O2诱导的内皮细胞损伤模型，体外模型证明丹七片促血管新生的药效；3）基于脂肪酸ß氧化的FAT/CD36-CPT1A通路，结合体内和体外模型，探究丹七片促进血管新生的作用机制。本课题选用丹七片为研究对象，运用药理学实验技术，从能量代谢角度深入探究丹七片促血管新生的机制及抗心肌缺血的作用，深化对冠心病发病机制的认识，为缺血性疾病的防治提供新的研究思路，对促进中药研究与临床治疗均具有重要意义。