Protect Effect And Mechanism Of A-01 On Myocardial Ischemia Injury

Objective: To investigate the protection of A-01 against myocardial ischemia injury and its possible pharmacological mechanism.Methods: Acute myocardial ischemia model was performed with left anterior descending (LAD) occlusion in rat heart. The effects of A-01 (dosage:5 mg/kg, 10 mg/kg, 20 mg/kg) on myocardial infarction and the activity of lactate dehydrogenase (LDH) in serum of rats with myocardial ischemia were observed. The subacute myocardial ischemia model was made by administration of isoproterenol (ISO), 50 mg/kg subcutaneously, for 2 consecutive days to induce myocardial injury. Cardiac indexe was determined, LDH in serum and the level of superoxide dismutase (SOD), malondialdehyd (MDA) in heart tissue of myocardial ischemia rats were assayed and pathological examination of the heart tissues were performed. Coagulate time (CT) was measured by glass method sheet, hemorheology was measured with heparin as anticoagulant, turbidimetric method was used to estimate platelet aggregation, so as to investigate the effect of A-01 on myocardial ischemia injury.Results: The myocardial ischemia size and the LDH in serum was markedly decreased by A-01 (dosage:5 mg/kg, 10 mg/kg, 20 mg/kg) in the myocardial ischemia model. A-01 could significantly decrease the increased level of LDH in animals with myocardial injury induced by ISO. In the heart administered ISO the superoxide dismutase (SOD) was decreased but the contents of malondialdehyd (MDA) were increased. Pre-treatment with A-01 could attenuate the changes of both SOD and MDA. Gravimetric parameter of heart was elevated by injecting ISO, A-01 was found to significantly reduce the gravimetric parameters when compared to ISO-group, the pathohistological changes ISO-induced were also ameliorated by A-01. The A-01 could obviously prolong the clotting time, inhibit platelet aggregation, and decrease the whole blood viscosity in low, middle and high shear rate and blood plasma viscosity.Conclusion: The A-01 could protect against myocardial ischemia injury in the way of enhancing antioxidative potency of the heart, inhibiting lipid peroxidation, improving hemorheology, blood viscosity, inhibiting platelet aggregation and so on.