基于氧化应激相关酶抑制活性的黄檀属植物抗缺血性心脏病新黄酮的发现及构效关系研究

Under the ischemic heart disease (coronary heart disease) , the myocardial cell injury caused mainly by restoration of oxygen and blood in the myocardium , during myocardial ischemia reperfusion. When oxidative stress reaction occurred during myocardial ischemia reperfusion, several enzymes , which could product free radicals, are activated. Then, The free radicals lead to occur imbalance of the anaerobic metabolism. Furthermore, myocardium is injured. Our previous research results is that as the characteristic components of Dalbergia L. f. (Leguminosae)， neoflavonoids have better protective effect on myocardium injury than other flavonoids in the Dalbergia odorifera . But, the free radical scavenging ability of neoflavonoids is weaker than the ability of other components in the plant. So, we guess that neolavonoids could have good protective effect on myocardium injury, because of the activity of several enzymes inhibited during oxidative stress reaction. We will choose several plants from Dalbergia L. f., as the research object. The neoflavonoids are prepared from these plants by the chemical method. Some enzymes are found by comparing neoflavonoids inhibiting the activity of several enzymes about oxidative stress reaction at the cell level and molecular level. On the base, we could build the structure-activity relationship between neoflavonoids and the enzyme about oxidative stress reaction ,by using "Molecular Docking combining with CoMFA and CoMSIA". Then, at the cell level and whole animal level, some neoflavonoids, which have good effect on inhibiting the activity of the enzyme about oxidative stress reaction, are verified.。At last, The mechanisms of the function of neoflavonoids are completely known, in order to provide evidence for the structure optimization of neoflavonoids.

心肌缺血/再灌注时血氧的恢复是引起缺血性心脏病（冠心病）心肌细胞损伤的主要原因。当心肌缺血/再灌注时，激活氧化应激相关酶，发生氧化应激反应，出现氧代谢失衡，导致大量自由基产生，进而损伤心肌。本课题组前期研究发现：降香黄檀中新黄酮类（黄檀属植物特有的成分）较其它黄酮类成分具有更好的抗心肌缺血损伤作用，但在清除自由基的能力上，却与其他黄酮类成分相近。表明新黄酮类可能还通过抑制氧化应激相关酶的活性而保护心肌。基于此，本课题拟选取多种黄檀属植物作为研究对象，提取分离一系列新黄酮类化合物。通过分子与细胞实验考察该类化合物对氧化应激相关酶的抑制作用，确定相关的氧化应激酶和有效成分。在此基础上，利用分子对接技术结合CoMFA模型和CoMSIA模型，构建基于氧化应激相关酶抑制活性的新黄酮类化合物的构效关系。再利用细胞和整体动物实验进行验证，从而阐明其作用机制，也为该类化学成分的结构优化提供依据。