NMR-Based Metabonomic Analysis Of Allium Macrostemon Bunge As A Treatment For Acute And Chronic Myocardial Ischemia In Rats

Myocardial ischemia (MI) refers to a pathological state of heart caused by the reduction of cardiac blood perfusion, which leads to the decrease of the heart’s oxygen supply and the abnormality of the myocardial energy metabolism. As two forms of MI, acute myocardial ischemia (AMI) and chronic myocardial ischemia (CMI) have posed a significant health risk for human beings. Allium Marostemon Bunge (AMB) is a popular traditional Chinese medicine for MI treatment. To understand the detailed mechanisms of AMB in treating MI and assess the therapeutic effects of this kind of traditional Chinese medicine, we characterized the metabonomic variations in rats, applying nuclear magnetic resonance (NMR) spectroscopy combined with multivariate statistical analysis. The main work contains the following aspects:1. Heart operation was applied to get AMI model, and combined with sham surgery group and AMI-pretreated group, more than30metabolites were detected including saccharides, amino acids, organic acids, choline and so on. Principal Components Analysis (PCA) and Orthogonal Projection to Latent Structure Discriminate Analysis (OPLS-DA) were conducted on1H NMR spectra of rat serum. Results showed that AMI not only aroused some physiological changes, but also led to the metabolic disorders in rats, which were related to the promotion of glycolysis, disruption of amino acid metabolism, promotion of lipid peroxidation and activation of p38MAPK. As a pre-treatment drug, AMB could reduce the injury from AMI and maintain metabolic balance, probably through cutting its energy consumption effectively, regulating amino acid metabolism and Ca2+overload, inhibiting the activity of p38MAPK. These findings provide comprehensive insights on the metabolic responses of AMB, which is important in the usage of AMB in AMI therapy.2. Injection of Isoproterenol hydrochloride was applied to get CMI model, and combined with sham surgery group and AMI-treated group,41metabolites were assigned in rat serum, including glucose, amino acids, organic acids, choline metabolites and so on From the fixed slides examined under a light microscope, CMI group exhibited CMI-induced histological damage, such as interstitial broadening, myofilament fracture, myocardial fiber disorder, sarcoplasmic dissolution, vacuolization formation, mitochondria swelling. To get the detailed metabonomic information, PCA and OPLS-DA were conducted on1H NMR spectra of rat serum. Similar to AMI, CMI also could simulate some physiological changes and create metabolic disorders in rats. After AMB treatment, the extent of CMI damage slowed down. To our knowledge, AMB might work through changing energy metabolism, adjusting amino acid metabolism, regulating Ca2+overload and so on.All these results show that NMR-based metabonomic analysis is a useful tool to study MI-related pathway and provides a new methodological way for systematically dissecting the underlying efficacies and mechanisms of AMB in treating MI.