Metabolomic Studies On Myocardial Ischemia Rats Intervented By Compound Danshen Dripping Pills

Coronary heart disease(CHD) is caused by atherosclerotic coronary artery stenosis, leading to insufficient blood supply of coronary and myocardial ischemia which will result in heart attack. Currently, CHD has become the third cause of death in China. Western medicine usually treat it with nitric acid lipids, calcium antagonists and beta-blockers, but there are some side-effects, such as dizziness, flushing and low blood pressure. With little side effects and significant effect, Traditional Chinese Medicine(TCM) is getting increasing attention in current researches.Compound Danshen dripping pills(CDDP) are developed based TCM theory and modern preparation technologies. With its multi-component, multi-link and multi-target characters, CDDP got tremendous employment in the prevention and treatment of CHD in clinic. The evaluation of the whole effect of CDDP, however, still lack a overall system and standards to reflect. The appearance of metabolomics has provided an opportunity for the resolution of this issue.With the technology of metabolomics, this paper studied the change of endogenous metabolites by ischemic myocardium resulted from coronary ligation in rats. By explaining the mechanism of myocardial ischemia on the body from the perspective of the overall metabolic network, the CDDP are evaluated. Combined with conventional pharmacological approaches, we tried a comprehensive understanding of the hazards of myocardial ischemia from the perspective of metabolic pathway, clarified the mechanism of CDDP interfering myocardial ischemia, and established a metabolomics approach to evaluate drug effect. The main content and the results are as follows:In this study, we made coronary artery ligation to establish and copy the rat model of myocardial ischemia, which is similar to the clinical disease. By measuring body weight, heart weight, heart-body ratio, CK in plasma, MDA and SOD in tissue, as well as the myocardial morphology, we investigated the influences on myocardial ischemia caused by coronary artery ligation. We also treated rats with CDDP, and evaluated its effect on the mechanism of anti-oxidative and anti-free radical. The result showed that CDDP have excellent effects: anti-oxygen-radicals, anti-oxidative-damage and protection of myocardial cells. Based on this, we studies the endogenous metabolites in the plasma and urine of rats with metabolomics. By the comparison of sham group, model group and model+CDDP group, and the difference between the 3rd day and the 28th day after modeling and treating, we found that myocardial ischemia leaded by ligation is closely related to energy metabolism, glucose metabolism, glutathione metabolism, lactose metabolism and ABC transporter, etc. In the plasma of rats, 2-butenedioic acid, succinic acid, l-threonine, creatinine, l-aspartic acid, l-isoleucine, citric acid, d-glucose, urea and so on had significant changes before and after myocardial ischemia. In the urine of rats, glycine, tetradecanoic acid, d-glucose, octadecanoic acid, uric acid, l-proline, d-fructose, aminomalonic acid, l-threonine and others made differences. However, with the administration of CDDP, rat endogenous metabolites have different degrees of correction, which shows that the active ingredient of the CDDP helped to change the level of metabolites and improve the metabolism networks, which leads to decreasing myocardial oxygen consumption, regulating myocardial energy metabolism, and protecting myocardial cells.